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This article appears in the November 7, 2013 issue of AICR's eNews.

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Editorial: A structured approach to uncommon cancers: what should a clinician do?

Abstract

In this issue of Annals of Oncology, Pecuchet et al. [1] have produced an elegant, original paper describing an innovative approach to the management of metastatic collecting duct carcinoma, using bevacizumab, gemcitabine and a platinum complex. They have shown surprising anticancer activity, which appears to have been sustained. They have addressed the usual concerns about case selection bias, positive response bias and pathology review of an uncommon tumor, and thus, this regimen certainly will bear confirmatory testing in other structured trials, especially as this triplet really does seem to give a different result from the more conventional gemcitabine–cisplatin combination or the established MVAC regimen (notwithstanding the absence of level 1 data at this time).

The editorial review of this manuscript raised an important generic question, viz. what should a clinician do when approaching a patient with a truly uncommon or rare tumor? Using a cut-off figure of 15 new cases/100 000 of population per year as a definition for ‘rare cancers’, Greenlee et al. [2] have suggested that these tumors cumulatively account for around 25% of incident cases in the United States. This figure seems inflated to me, because of their cut-off value, especially as I do not view testicular cancer as a rare tumor (yet it has an incidence of 6.8/100 000 males per year). Nonetheless, Greenlee et al. make an important point—rare tumors cumulatively do constitute a significant proportion of the total cancers presenting, yet we have remarkably little information available to guide management, when compared with the common tumors that arise in breast, lung, prostate, colon, pancreas and bladder. A similar situation appears to apply to oncology practice in Europe, in a report using a cut-off of less than six new cases/100 000 of population per year, with the accompanying suggestion …...

[Full Text of this Article requires $$$) 

Hereditary Cancer - Jewish Genetic Disorders

Center for Jewish Genetics

Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA

abstract

Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS [56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low-malignant potential (LMP) serous, and 24 for invasive serous EOC], selected using pre-defined criteria.

Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95 % confidence intervals are reported. Nine variants tagging six loci were associated with subtype-specific EOC risk at P < 0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR = 1.17, P = 0.029, n = 1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P = 0.014, n = 2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR = 0.86, P = 0.0043, n = 892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR = 0.84, P = 0.0007) and LMP serous EOC risk remained statistically significant at P < 0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes.

 

Platinum versus platinum-combination chemotherapy in platinum-sensitive recurrent ovarian cancer: a meta-analysis using individual patient data

abstract

BACKGROUND:

The majority of women with ovarian cancer develop recurrent disease. For patients with a platinum-free interval of >6 months, platinum-based chemotherapy is a treatment of choice. The benefit of platinum-based combination chemotherapy in randomized trials varies, and a meta-analysis was carried out to gain more secure information on the size of the benefit of this treatment.

MATERIALS AND METHODS:

We initiated a systematic review and meta-analysis following a pre-specified protocol to determine whether combination chemotherapy is superior to single-agent platinum chemotherapy in women with relapsed platinum-sensitive ovarian cancer.

RESULTS:

A total of five potentially eligible randomized trials were identified that had used combination-platinum chemotherapy versus single-agent platinum chemotherapy in women with relapsed platinum-sensitive ovarian cancer. For one trial (190 patients), adequate contact with the investigators could not be established. Therefore, four trials that randomly assigned 1300 patients were included, with a median follow-up of 36.1 months. Overall survival (OS) analyses were based on 865 deaths and demonstrated evidence for the benefit of combination-platinum chemotherapy (HR = 0.80; 95% CI, 0.64-1.00; P = 0.05). Progression-free survival (PFS) analyses were based on 1167 events and demonstrated strong evidence for the benefit of combination-platinum chemotherapy (HR = 0.68; 95% CI, 0.57-0.81; P < 0.001). There was no evidence of a difference in the relative effect of combination-platinum chemotherapy on either OS or PFS in patient subgroups defined by previous paclitaxel (Taxol) treatment (OS, P = 0.49; PFS, P = 0.66), duration of treatment-free interval (OS, P = 0.86; PFS, P = 0.48) or the number of previous lines of chemotherapy (OS, P = 0.21; PFS, P = 0.27).

CONCLUSIONS:

In this individual patient data (IPD) meta-analysis, we have demonstrated that combination-platinum chemotherapy improves OS and PFS across all subgroups. This provides the strongest evidence to date of the benefit of combination-platinum over single-agent platinum.

 

Single-Port Laparoscopic Extraperitoneal Para-aortic Lymphadenectomy

abstract

Objective: The aim of this study was to evaluate the feasibility and the safety of single-port extraperitoneal laparoscopic para-aortic lymphadenectomy for patients with gynecologic cancer.

Methods: From July 2012 to January 2013, a total of 7 patients with gynecologic cancer underwent a laparoscopic pelvic and para-aortic lymphadenectomy with a single-port device. An extraperitoneal approach was performed for para-aortic lymphadenectomy using only one 2.5-cm incision on the left side. In 6 patients, additionally, hysterectomy and pelvic lymphadenectomy with conventional laparoscopy were performed to complete the treatment.

Results: Aortic dissection was complete in all cases without complications. The median age of the patients was 63 years (range, 48–78 years), and the median patient body mass index was 31 kg/m² (range, 19–38 kg/m²). The median number of para-aortic nodes was 17 (range, 10–25); the median operative time was 204 minutes (range, 120–300 minutes). The median hospital stay was 4 days (range, 3–6 days). No patient encountered postoperative complications.

Conclusions: This study demonstrates the feasibility of single-port laparoscopic (youtube) extraperitoneal para-aortic lymphadenectomy.

 

Incidence and Predictors of Venous Thromboembolism After Debulking Surgery for Epithelial Ovarian Cancer

abstract
 

Objective: The aim of this study was to determine the incidence and the risk factors of venous thromboembolism (VTE) within 30 days after primary surgery for epithelial ovarian cancer (EOC).

Methods: In a historical cohort study, we estimated the postoperative 30-day cumulative incidence of VTE among consecutive Mayo Clinic patients undergoing primary cytoreduction for EOC between January 2, 2003, and December 29, 2008. We tested perioperative patient characteristics and process-of-care variables (defined by the National Surgical Quality Improvement Program, >130 variables) as potential predictors of postoperative VTE using the Cox proportional hazards modeling.

Results: Among 569 cases of primary EOC cytoreduction and/or staging and no recent VTE, 35 developed symptomatic VTE within 30 days after surgery (cumulative incidence = 6.5%; 95% confidence interval, 4.4%–8.6%). Within the cohort, 95 (16.7%) received graduated compression stockings (GCSs), 367 (64.5%) had sequential compression devices + GCSs, and 69 (12.1%) had sequential compression devices + GCSs + postoperative heparin, with VTE rates of 1.1%, 7.4%, and 5.8%, respectively (P = 0.07, χ² test). The remaining 38 (6.7%) received various other chemical and mechanical prophylaxis regimens. In the multivariate analysis, current or past tobacco smoking, longer hospital stay, and a remote history of VTE significantly increased the risk for postoperative VTE.

Conclusions: Venous thromboembolism is a substantial postoperative complication among women with EOC, and the high cumulative rate of VTE within 30 days after primary surgery suggests that a more aggressive strategy is needed for VTE prevention. In addition, because longer hospital stay is independently associated with a higher risk for VTE, methods to decrease length of stay and minimize factors that contribute to prolonged hospitalization are warranted.

 

A Phase 2 Study of Oxaliplatin Combined With Continuous Infusion Topotecan for Patients With Previously Treated Ovarian Cancer

Abstract

Background: Phase 2 trials suggest that prolonged intravenous (IV) infusion of the topoisomerase 1 inhibitor topotecan may be less toxic than when given by standard IV bolus 5-day administration. Oxaliplatin exhibits efficacy in platinum-pretreated disease and shows preclinical synergy with topoisomerase 1 inhibitors. We sought to determine the efficacy and safety of oxaliplatin plus infusion topotecan in recurrent platinum-pretreated ovarian cancer.

Methods: Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancers previously treated with 1 to 2 prior regimens including platinum and taxane received oxaliplatin (85 mg/m² day 1 and day 15) and topotecan (0.4 mg/m² per day) by continuous IV infusion over 14 days every 4 weeks. The primary objective of the trial was to estimate the objective response rate in platinum-resistant disease (stratum 1) and in platinum-sensitive disease (stratum 2). Toxicities were assessed in all patients.

Results: Thirty-eight patients received 144 cycles of therapy (median, 4; range, 1–6). The most common grade 3 and grade 4 toxicities included thrombocytopenia (grade 3, 37%; and grade 4, 19%), neutropenia (grade 3, 37%; grade 4, 11%), and anemia (grade 3, 15%). Response occurred in 4 of 19 patients in stratum I (21%; 95% confidence intervals, 6%–46%) and 9 of 19 patients in stratum 2 (47%; 95% CI, 24%–71%). Three in each stratum had lengthy complete responses.

Conclusions: Biweekly oxaliplatin plus a 14-day continuous IV infusion of topotecan, given monthly, is an active regimen in platinum-pretreated ovarian cancer and merits additional evaluation.

 

Clinical Outcome of Isolated Serous Tubal Intraepithelial Carcinomas (STIC)

abstract

Objective: Risk-reducing salpingo-oophorectomy (RRSO) is recommended for women with BRCA mutation due to increased risk of pelvic serous carcinoma. Serous tubal intraepithelial carcinoma (STIC) is a pathologic finding of unknown clinical significance. This study evaluates the clinical outcome of patients with isolated STIC.

Materials/Methods: We retrospectively reviewed the medical records of consecutive patients with a germline BRCA1/2 mutation or a high-risk personal or family history of ovarian cancer who underwent RRSO between January 2006 and June 2011. All patients had peritoneal washings collected. All surgical specimens were assessed using the sectioning and extensively examining the fimbria protocol, with immunohistochemistry when indicated. p53 signature lesions and secretory cell outgrowths were excluded.

Results: Of 593 patients who underwent RRSO, isolated STIC was diagnosed in 12 patients (2%). Five patients (42%) were BRCA1 positive, 5 patients (42%) were BRCA2 positive, and 2 patients (17%) had high-risk family history. Preoperatively, all patients with STIC had normal CA-125 levels and/or pelvic imaging results. Seven patients underwent hysterectomy and omentectomy, 6 patients (46%) had pelvic node dissections, and 5 patients (39%) had para-aortic node dissections. With the exception of positive peritoneal washings in 1 patient, no invasive or metastatic disease was identified. No patient received adjuvant chemotherapy. At median follow-up of 28 months (range, 16–44 months), no recurrences have been identified.

Conclusions: Among the cases of isolated STIC after RRSO reported in the literature, the yield of surgical staging is low, and short-term clinical outcomes are favorable. Peritoneal washings are the most common site of disease spread. Individualized management is warranted until additional data become available.

 

The Inverse Relationship between 25-Hydroxyvitamin D and Cancer Survival: Discussion of Causation

Free Full-Text 

 "The best information that we have on disease severity is stage at the time of diagnosis. Most studies included in this review have taken disease severity into account in the analyses, e.g., using stage or other known prognostic factors (Table 1). Generally, these adjustments have had little effect on the relationship between 25-OHD level and cancer survival."

(ovarian cancer) reference:
Schwartz, G.G.; Skinner, H.G. Prospective studies of total and ionized serum calcium in relation to incident and fatal ovarian cancer. Gyn. Oncol. 2013, 129, 169–172.

Saturday, January 19, 2013 (prior blog posting)

Prospective Studies of Total and Ionized Serum Calcium in Relation to Incident and Fatal Ovarian Cancer.

Source

Departments of Cancer Biology, Urology, and Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina. Electronic address: gschwart@wakehealth.edu.

Abstract

OBJECTIVE:

Biological markers that could aid in the detection of ovarian cancer are urgently needed. Many ovarian cancers express parathyroid hormone-related protein, which acts to raise calcium levels in serum. Thus, we hypothesized that high serum calcium levels might predict ovarian cancer.

METHODS:

We examined associations between total and ionized serum calcium and ovarian cancer mortality in the Third National Health and Nutrition Survey (NHANES III) using Cox proportional hazard models. We then examined associations of serum calcium with incident ovarian cancer in a second prospective cohort, the NHANES Epidemiological Follow-up Study (NHEFS).

RESULTS:

There were eleven deaths from ovarian cancer over 95,556 person-years of follow-up in NHANES III. After multivariable adjustment, the risk for fatal ovarian cancer was 52% higher for each 0.1mmol/L increase in total serum calcium (RH=1.52, 95% CI 1.06 - 2.19) and 144% higher for each 0.1mmol/L increase in ionized serum calcium (RH=2.44, 95% CI=1.45 - 4.09). Associations persisted after adjusting for nulliparity and the use of oral contraceptives. Eight incident ovarian cancers occurred over 31,089 person-years of follow-up in the NHEFS. After adjusting for covariates, there was a 63% higher risk for ovarian cancer with each 0.1mmol/L increase in total serum calcium (95% CI 1.14 - 2.34). Similar results were observed for albumin-adjusted serum calcium.

CONCLUSIONS:

Higher serum calcium may be a biomarker of ovarian cancer. This is the first report of prospective positive associations between indices of calcium in serum and ovarian cancer. Our findings require confirmation in other cohorts.

Traumatization and chronic pain: a further model of interaction

open access

Up to 80% of patients with severe posttraumatic stress disorder are suffering from “unexplained” chronic pain. Theories about the links between traumatization and chronic pain have become the subject of increased interest over the last several years. We will give a short summary about the existing interaction models that emphasize particularly psychological and behavioral aspects of this interaction. After a synopsis of the most important psychoneurobiological mechanisms of pain in the context of traumatization, we introduce the hypermnesia–hyperarousal model, which focuses on two psychoneurobiological aspects of the physiology of learning. This hypothesis provides an answer to the hitherto open question about the origin of pain persistence and pain sensitization following a traumatic event and also provides a straightforward explanatory model for educational purposes.

 Keywords: posttraumatic stress disorder, chronic pain, hypermnesia, hypersensitivity, traumatization

"...We consider that the psychotherapeutically desirable step of reframing is strongly supported by our model: for patients, it is therapeutically very meaningful to conceive trauma-associated sequelae as a “normal” reaction to an extremely “abnormal” event.... 

Resistance Is Futile: Chemists Develop New Way to Kill Cancer Cells Resistant to the Chemotherapy Drug Cisplatin

medical news

Saving Ears and Kidneys from Cisplatin

open access (technical)

 

Metabolic complications with the use of mTOR inhibitors for cancer therapy

abstract

Interpretation

The risk of all grade and grade 3–4, hyperglycemia, hypercholesterolemia, and hypertriglyceridemia, are increase in patients treated with mTOR inhibitors compared with control.

 

A phase I study of the combination of ro4929097 and cediranib in patients with advanced solid tumours (PJC-004/NCI 8503)

open access

 Background: 

The Notch signalling pathway has been implicated in tumour initiation, progression, angiogenesis and development of resistance to vascular endothelial growth factor (VEGF) targeting, providing a rationale for the combination of RO4929097, a γ-secretase inhibitor, and cediranib, a VEGF receptor tyrosine kinase inhibitor.

"This was an open-label, dose escalation phase I trial. It followed the standard 3+3 rule and no intra-patient dose escalation was allowed. Initial design of study consisted of two stages: (1) dose escalation and (2) expansion cohort, including patients with breast cancer, malignant melanoma, colorectal cancer, pancreatic cancer, renal cancer, high-grade glioma, non-small cell lung cancer, or ovarian cancer. However, accrual was terminated on 7 April 2012, after completion of three dose levels (DLs), due to discontinuation of RO4929097 development. Patients who were felt to be deriving clinical benefit were allowed to remain on cediranib monotherapy on study. The trial was approved by all relevant institutional ethical committees.....

 

(U.S.) ACR Appropriateness Criteria Staging and Follow-up of Ovarian Cancer

Abstract

Purchase this article for 30.00 USD 

---

Imaging is used to detect and characterize adnexal masses and to stage ovarian cancer both before and after initial treatment, although the role for imaging in screening for ovarian cancer has not been established. CT and MRI have been used to determine the resectability of tumors, the candidacy of patients for effective cytoreductive surgery, the need for postoperative chemotherapy if debulking is suboptimal, and the need for referral to a gynecologic oncologist. Radiographic studies such as contrast enema and urography have been replaced by CT and other cross-sectional imaging for staging ovarian cancer. Contrast-enhanced CT is the procedure of choice for preoperative staging of ovarian cancer. MRI without and with contrast may be useful after equivocal CT, but is usually not the best initial procedure for ovarian cancer staging. Fluorine-18-2-fluoro-2-deoxy-D-glucose–PET/CT may not be needed preoperatively, but its use is appropriate for detecting and defining post-treatment recurrence. Ultrasound is useful for evaluating adnexal disease, but has limited utility for staging ovarian cancer.

The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.


Figures and tables from this article: (requires paid subscription)

Variant 1. Pretreatment staging of ovarian cancer. (See narrative for comments regarding CA-125.)

Rating scale: 1, 2, 3 = usually not appropriate; 4, 5, 6 = may be appropriate; 7, 8, 9 = usually appropriate.

Napsin A as a marker of clear cell ovarian carcinoma

open access

Background

Clear cell carcinomas are aggressive tumors with a distinct biologic behaviour. In a genome-wide screening for genes involved in chemo-resistance, NAPA was over-expressed in cisplatin-resistant cells. The NAPA (protein) Napsin A was described to promote resistance to cisplatin by degradation of the tumor suppressor p53.

Methods

Totally 131 patients were included in this study all in FIGO-stages I-II; 16 were clear cell tumors which were compared with 40 Type I tumors and 75 type II tumors according to the markers Napsin A, p21, p53 and p27 and some clinical features. For detection of the markers tissue microarrays and immunohistochemistry were used.

Results

Positivity for Napsin A was detected in 12 (80%) out of the 15 clear cell tumors available for analysis compared with 3 (4%) out of the Type I and II tumors in one group (p < 0.001). Differences in p21 status, p53 status, and p21 + p53- status were striking when clear cell tumors were compared with Type I, Type II, and Type I and II tumors in one group, respectively. The p21 + p53-status was associated to positive staining of Napsin A (p = 0.0015) and clear cell morphology (p = 0.0003). In two separate multivariate logistic regression analyses with Napsin A as endpoint both clear cell carcinoma with OR = 153 (95% C.I. 21--1107); (p < 001) and p21 + p53- status with OR = 5.36 (95% C.I. 1.6-17.5); (p = 0.005) were independent predictive factors. ROC curves showed that AUC for Napsin A alone was 0.882, for p21 + p53- it was 0.720 and for p21 + p53-Napsin A + AUC was 0.795. Patients with clear cell tumors had lower (p = 0.013) BMI than Type I patients and were younger (p = 0.046) at diagnosis than Type II patients. Clear cell tumors had a higher frequency (p = 0.039) of capsule rupture at surgery than Type I and II tumors.

Conclusions

Positivity of Napsin A in an epithelial ovarian tumor might strengthen the morphological diagnosis of clear cell ovarian carcinoma in the process of differential diagnosis between clear cell ovarian tumors and other histological subtypes.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

"...Our findings related to the clinico-pathological differences are supported by earlier studies[4,7,10] but results about the immunohistochemical profile for Napsin A is new. Clear cell carcinomas resembles Type I tumors based on relative genetic stability and

frequent presentation in stage I, but on the other hand, clear cell carcinoma is high grade at diagnosis. Furthermore, wild-type p53 is mostly present and mutations are uncommon in clear cell tumors contrary to Type II tumors, which are genetically unstable and have a highrequency of p53 mutations [10,11]. Ovarian clear cell carcinomas constitute a heterogeneous disease at the genomic level despite having similar histological

features. Previous data fromTan et al [11] has suggested that the pattern of genome-wide copy number aberrations may predict clinical outcome... 

Privacy and All That (sharing)

NEJM (requires paid subscription to view)

 

Perspective

Privacy and All That

"The two men had sat in neighboring chemotherapy chairs, swapping tales of side effects, antiemetics, their childhoods, religion. When one died, it affected the other profoundly. But there's no protocol for sharing information with patients about their fellow travelers."

Top 50 Concerns, Questions and Comments From Anesthesia Techs

Anesthesia Techs

Patient Portals Increase Access And Reduce Misinformation

Diagnostic Imaging

Already gaining popularity in health systems nationwide, patient portals could now play a more significant role in radiology by automatically structuring and combining radiology reports with related imaging studies. This integration would give patients greater access to helpful information about their health status.

In a study published in the November issue of the Journal of the American Medical Informatics Association, the University of California-Los Angeles developed as web-based patient portal for individuals with brain cancer.

Allowing patients to view their radiology reports makes sense even if patients can’t fully understand the studies, the authors wrote, because the patient interest is there.

“Even though radiology test results are one of the most difficult portions of the clinical record for lay people to understand, they are one of the most frequently accessed pieces of information via patient portals when available,” they wrote.

- See more at: http://www.diagnosticimaging.com/pacs-and-informatics/patient-portals-increase-access-and-reduce-misinformation#sthash.KubvbFbT.dpuf

 

Imaging informatics for consumer health: towards a radiology patient portal

Abstract

Objective With the increased routine use of advanced imaging in clinical diagnosis and treatment, it has become imperative to provide patients with a means to view and understand their imaging studies. We illustrate the feasibility of a patient portal that automatically structures and integrates radiology reports with corresponding imaging studies according to several information orientations tailored for the layperson.

Methods The imaging patient portal is composed of an image processing module for the creation of a timeline that illustrates the progression of disease, a natural language processing module to extract salient concepts from radiology reports (73% accuracy, F₁ score of 0.67), and an interactive user interface navigable by an imaging findings list. The portal was developed as a Java-based web application and is demonstrated for patients with brain cancer.

Results and discussion The system was exhibited at an international radiology conference to solicit feedback from a diverse group of healthcare professionals. There was wide support for educating patients about their imaging studies, and an appreciation for the informatics tools used to simplify images and reports for consumer interpretation. Primary concerns included the possibility of patients misunderstanding their results, as well as worries regarding accidental improper disclosure of medical information.

Conclusions Radiologic imaging composes a significant amount of the evidence used to make diagnostic and treatment decisions, yet there are few tools for explaining this information to patients. The proposed radiology patient portal provides a framework for organizing radiologic results into several information orientations to support patient education.

 

This Guy’s Wife Got Cancer, So He Did Something Unforgettable The Free Thought Project

 Blogger's Note: thanks to FB for this, sad but real

The Free Thought Project

conference notice: 6th Familial Cancer Conference - Event - ESO

ESO

6th Familial Cancer Conference

05/06/2014 - 06/06/2014, Madrid, Spain

 

The combination of gemcitabine and carboplatin shows similar efficacy in the treatment of platinum-resistant and platinum-sensitive recurrent epithelial ovarian cancer patients

abstract

The aim of this study was to evaluate progression-free survival, overall survival (OS), response rate (RR), and clinical benefit in recurrent ovarian cancer patients treated with gemcitabine and carboplatin and to compare the outcome among platinum-resistant and platinum-sensitive patients. A retrospective study using the medical records of patients diagnosed and treated for recurrent epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma with gemcitabine and carboplatin from 2005 through 2012 at the Tel Aviv Sourasky Medical Center. The treatment regimen was carboplatin (area under the curve=5) administered on day 1 and gemcitabine 850 mg/m administered on days 1 and 8 in a 21-day cycle. Seventy patients with a median age of 57 years (range: 38-86) were included in the study. Most patients (94.3%) were initially diagnosed with stage III-IV disease and 44.3% had platinum-sensitive disease. Median progression-free survival in platinum-sensitive patients was 6.3 months [95% confidence interval (CI): 4.3-8.3] and 6.3 months (95% CI: 4.6-7.9) in platinum-resistant patients. Median overall survival was 15.8 months (95% CI: 13.6-18.1) in the platinum-sensitive patients and 18.4 months (95% CI: 10.0-27.8) in the platinum-resistant patients. Platinum-sensitive patients had a RR of 43.2% and platinum-resistant patients had a RR of 39.1%. The clinical benefit was 70.5% in platinum-sensitive patients and 65.2% in platinum-resistant patients. Overall treatment had a favorable safety profile. Gemcitabine and carboplatin demonstrate moderate toxicity with similar efficacy in both platinum-sensitive and platinum-resistant epithelial ovarian cancer, suggesting reversal of platinum resistance by gemcitabine.

 

Stereotactic radiosurgery in the treatment of brain metastases: The current evidence

open access

Introduction

According to conservative estimates about 8% of cancer patients will develop brain metastases,¹ which often cause the leading symptoms..... 

Destruction of the bladder by single dose Mitomycin C for low-stage transitional cell carcinoma (TCC) – avoidance, recognition, management and consent (Lynch syndrome patients note)

Blogger's Note: of interest to Lynch Syndrome patients with upper tract urothelial carcinoma (UTUC) and prophylaxis MMC to reduce the risk of bladder cancer after radical nephroureterectomy; note this study included bladder cancer patients

abstract

 Keywords:

• bladder perforation;
• intravesical mitomycin;
• consent;
• extravasation

Objectives

• To identify a cohort of patients under our care who have had significant and in some cases irreparable damage to their bladders after Mitomycin C (MMC) instillation.
• To highlight the importance of avoidance and recognition of bladder perforations during transurethral resection of bladder tumour (TURBT) and explore the issue of consent regarding MMC given the serious complications that may occur after its instillation.

Patients and Methods

• Patients referred to our tertiary centre for a second opinion to manage their complications after a suspected MMC leak was identified from the departmental database between January 2000 and December 2010.
• After collection of all the records, we established a cohort of six patients.
• All patients had their initial tumour resection elsewhere and were referred for specialist management thereafter. Details of the operating surgeon and cystoscopic findings were known only in half of the cases.
• Retrospective analysis of their notes including documentation from the referring centre was undertaken. This included a review of all the histology and imaging.

Results

• All patients had immediate severe pelvic pain on instillation of the MMC. Four of the six continue to have chronic pelvic pain.
• Two patients had urinary retention and three had severe lower urinary tract symptoms. One patient developed a frozen pelvis.
• Initial treatment was with an indwelling catheter for a period of 2–52 weeks to aid healing.
• Two patients had reconstructive surgery, one with success and the other with failure, as an intestinal patch failed to close the fistula and he continues with a catheter. One patient had an ileal conduit.
• No patient was warned of such complications.

Conclusions

• Although rare, prophylactic MMC can have devastating consequences.
• Patients should be aware of such major risks.
• Strong emphasis should be placed on the quality of the initial TURBT coupled with the judgement of an experienced surgeon before to MMC instillation. The real clinical benefit could be reviewed and intravesical MMC offered only to patients who have a good chance of benefit.

 

Patients Prefer to Insert NG Feeding Tubes Themselves: Study

medscape

Nov 2013 Scottish Intercollegiate Guidelines Network: Management of Epithelial Ovarian Cancer

open access


 Scottish Intercollegiate Guidelines Network

Management of epithelial ovarian cancer

A national clinical guideline

 

 

International Ovarian & Testicular Stromal Tumor Registry - Full Text View - ClinicalTrials.gov

Tumor Registry

Purpose

Rare tumors are understudied, yet have the potential to shed light on vast areas of cancer research. Ovarian sex cord-stromal tumors, rare tumors of childhood and young adulthood, have recently been found to be associated with a lung cancer of early childhood called pleuropulmonary blastoma (PPB). The cause of these ovarian tumors is unknown. DICER1 mutations are seen in the majority of children with PPB. Research shows DICER1 mutations are also seen in some patients with ovarian tumors. Like PPB, ovarian stromal tumors are highly curable when found in early stage; however, later forms of the disease are aggressive and often fatal. The International Ovarian Stromal Tumor Registry collects clinical and biologic data to understand why these tumors occur and how to treat them. Current work involves the study the role of DICER1 and miRNA expression in ovarian stromal tumors. Understanding the clinical history, predisposing factors and DICER1 and miRNA expression in these ovarian tumors of childhood will lead to targeted screening and risk stratification for evidence-based treatment and biologically rational therapies. These efforts will improve the lives of children by increasing survival and reducing late effects.

The specific goals of the International Ovarian and Testicular Stromal Tumor Registry are:

1. to understand risk factors by studying age, pathologic subtype, histopathologic features, tumor invasiveness, degree of differentiation, presence of metastasis
2. to collect information on personal and family history in order to refine the clinical characteristics of patients and families with and without germline DICER1 mutations and other genetic predisposing factors
3. to determine whether there is a pattern of gene expression or DNA alterations that correlate with predisposition to ovarian tumors, biologic behavior and clinical outcome
4. to determine optimal screening regimens
5. to use clinical data obtained through the Registry to refine treatment algorithms
6. to establish a collection of annotated biology specimens (tumor tissue and germline DNA) for future research

Condition
Ovarian Stromal Tumor Testicular Stromal Tumors Ovarian Small Cell Carcinoma

 

Can patient reported outcomes help identify the optimal outcome in palliative surgery?

abstract

Background

The purpose of this pilot study was to determine whether an open-ended questionnaire captures severe symptoms in cancer patients undergoing palliative surgical consultation that a structured, validated quality-of-life assessment does not capture.

Methods

We prospectively used the Functional Assessment of Cancer Therapy–General (FACT-G) and an open-ended questionnaire to assess the symptoms of patients with incurable malignancies who underwent palliative surgical consultation at our institution between January 2011 and September 2012.

Results

Of the 69 patients enrolled, the most common indications for consultation were bowel obstruction (54%), jaundice (13%), wound problems (10%), and gastrointestinal bleeding (7%). Of the severe symptoms patients reported, 76% were identified with the FACT-G alone, 22% were identified with the open-ended questionnaire alone, and 2% were duplicate responses captured with both the FACT-G and open-ended questionnaire. The open-ended questionnaire captured 68 instances of severe symptoms in 47 patients that the FACT-G did not capture; of these symptoms, 52 were considered to be highly relevant to surgery and potential outcome measures.

Conclusions

An open-ended questionnaire can identify severe symptoms that a global quality of life survey cannot capture and could be used in conjunction with a global survey to reassess symptoms after palliative surgical consultation. 

Clinical Research in Surgical Oncology: An Analysis of ClinicalTrials.gov

abstract

Background

The objective of this study was to provide a descriptive analysis of registered clinical trials in surgical oncology at ClinicalTrials.gov.

Methods

Data was extracted from ClinicalTrials.gov using the following search engine criteria: “Cancer” as Condition, “Surgery OR Operation OR Resection” as Intervention, and Non-Industry sponsored. The search was limited to Canada and the United States and included trials registered from January 1, 2001 to January 1, 2011.

Results

Of 9,961 oncology trials, 1,049 (10.5 %) included any type of surgical intervention. Of these trials, 125 (11.9 %, 1.3 % of all oncology trials) assessed a surgical variable, 773 (73.7 %) assessed adjuvant/neoadjuvant therapies, and 151 (14.4 %) were observational studies. Of the trials assessing adjuvant therapies, systemic treatment (362 trials, 46.8 %) and multimodal therapy (129 trials, 16.7 %) comprised a large focus. Of the 125 trials where surgery was the intervention, 59 trials (47.2 %) focused on surgical techniques or devices, 45 trials (36.0 %) studied invasive diagnostic methods, and 21 trials (16.8 %) evaluated surgery versus no surgery. The majority of the 125 trials were nonrandomized (72, 57.6 %).

Conclusions

The number of registered surgical oncology trials is small in comparison to oncology trials as a whole. Clinical trials specifically designed to assess surgical interventions are vastly outnumbered by trials focusing on adjuvant therapies. Randomized surgical oncology trials account for <1 % of all registered cancer trials. Barriers to the design and implementation of randomized trials in surgical oncology need to be clarified in order to facilitate higher-level evidence in surgical decision-making.

 

Is it possible to diagnose malignancy from fluid in cystic ovarian tumors?

abstract

Objective

p53 gene mutations are frequently identified in ovarian cancer tissue. The aim of this study was to investigate whether wild type or mutated genomic DNA can be identified in ovarian cystic fluid specimens.

Study design

Forty-eight Japanese patients with cystic ovarian tumors (30 benign cysts, 8 borderline malignant tumors, and 10 cancers) were investigated. Cystic fluid and tumor tissue were obtained during surgery......

Conclusion

In cystic ovarian tumors, cystic fluid may provide informative material for molecular studies since it reflects the p53 status of tumor tissue in the cyst wall. This system might help to identify ovarian malignancy without resection of the tumor tissues.
 

DNA barcoding detects contamination and substitution in North American herbal products

open access

Conclusions:

Most of the herbal products tested were of poor quality, including considerable product substitution, contamination and use of fillers. These activities dilute the effectiveness of otherwise useful remedies, lowering the perceived value of all related products because of a lack of consumer confidence in them. We suggest that the herbal industry should embrace DNA barcoding for authenticating herbal products through testing of raw materials used in manufacturing products. The use of an SRM DNA herbal barcode library for testing bulk materials could

provide a method for best practices in the manufacturing of herbal products.This would provide consumers with safe, high quality herbal products.

Table 1 DNA barcode results listed for individual samples from blind testing of the 44 herbal products and 50 herbal

leaf samples representing 42 medicinal species of plan

Figure 3

DNA barcode results from blind testing of the 44 herbal products representing 12 companies (fillers, substitutions, contaminents, authentic)

 

Herbal Supplements Are Often Not What They Seem

NYTimes.com

Viewing Laboratory Test Results Online: Patients’ Actions and Reactions | Journal of Participatory Medicine

open access

Conclusion: This study demonstrates that patients who view their lab test results online overwhelmingly react with positive rather than negative emotions. The results also illustrate the influence of physician-patient prior communication on patients’ reactions and their followup actions. 

Table 3. Reactions when viewing test results online.

How to Pronounce Epithelial Ovarian Cancer - YouTube (english language)

youtube

How to help women with ovarian cancer advocate for their health- Make Guru

video

Dr. Birrer on Other Targets in Ovarian Cancer - video

 video

Dr. Thigpen on Ovarian Cancer Agents Not Approved by the FDA - video

 video

Duavee - Menopause: FDA OKs Drug to Treat Hot Flashes in Menopausal Women

medical news

Menopause - New Analysis Confirms Hormone Therapy Won't Prevent Disease After Menopause

medical news (read the whole article)

"...She noted that some doctors seem to have had a "misunderstanding" regarding the original WHI findings, and are reluctant to use hormone therapy even for hot flashes.... 

Molecular Pathways: Estrogen Pathway in Colorectal Cancer

Blogger's Note: does not relate to Lynch Syndrome women; for those who have had an interest in and/or followed the WHI trial and subsequent analyses; when the initial WHI trial was publicized very little attention was paid to this particular aspect (eg. estrogen/hrt/risk reduction); debatable if and/or when 'we' will ever get to an analysis in affected Lynch Syndrome women (eg. low numbers etc.)

abstract

"Worldwide, colorectal cancer has a higher incidence rate in men than in women, suggesting a protective role for sex hormones in the development of the disease. Preclinical data support a role for estrogen and its receptors in the initiation and progression of colorectal cancer and establishes that protective effects of estrogen are exerted through ERβ. Hormone replacement therapy (HRT) in postmenopausal women as well as consumption of soy reduces the incidence of colorectal cancer. In the Women's Health Initiative trial, use of HRT in postmenopausal women reduced the risk of colon cancer by 56% [95% confidence interval (CI), 0.38–0.81; P = 0.003]. A recent meta-analysis showed that in women, consumption of soy reduced the risk of colon cancer by 21% (95% CI, 0.03–0.35; P = 0.026). In this review, using the preclinical data, we translate the findings in the clinical trials and observational studies to define the role of estrogen in the prevention of colorectal cancer. We hypothesize that sometime during the tumorigenesis process ERβ expression in colonocytes is lost and the estrogen ligand, HRT, or soy products, exerts its effects through preventing this loss. Thus, in the adenoma-to-carcinoma continuum, timing of HRT is a significant determinant of the observed benefit from this intervention. We further argue that the protective effects of estrogen are limited to certain molecular subtypes. Successful development of estrogen modulators for prevention of colorectal cancer depends on identification of susceptible colorectal cancer population(s). Thus, research to better understand the estrogen pathway is fundamental for clinical delivery of these agents."

 

Cancer Survivorship, a Unique and Growing Cohort in Medical Practice: Radiology Perspective

open access

Article Outline

• Abstract
• Pulmonary
• Genitourinary
• Musculoskeletal
• Gastrointestinal
• Monitoring for Recurrence
• Conclusions
• References

We will review the radiologic manifestation of the common consequences of cancer and its therapy. There are 2 general sequelae:

•Organ, tissue, or systemic damage related to therapy. Typically, this will include local scarring and inflammation due to surgery or radiation therapy. In addition, systemic therapy may cause inflammation, scarring, or necrosis in a broad range of target organs, including the lung, liver, kidneys, brain, and peripheral nerves.

•Emergence of a new cancer site: This will most frequently represent late-recurrence of the initial treated tumor. However, second primary cancers may result from the same underlying germline mutation that produces the original tumor (eg, ovarian cancer in BRCCA1 mutations) or as a result of mutagenic effects of radiation or chemotherapy.

 

Table. Summary of Some of the Available Imaging Modalities for Common Diagnoses in Oncologic Patients

Folcalin/Dexmethylphenidate: MedlinePlus Drug Information

Drug Information

Symcat Symptom Checker

free to try-registration not required

The impact of perioperative packed red blood cell transfusion on survival in epithelial ovarian cancer

abstract

OBJECTIVE:

Perioperative packed red blood cell transfusion (PRBCT) has been implicated as a negative prognostic marker in surgical oncology. There is a paucity of evidence on the impact of PRBCT on outcomes in epithelial ovarian cancer (EOC). We assessed whether PRBCT is an independent risk factor of recurrence and death from EOC.

METHODS:

Perioperative patient characteristics and process-of-care variables (defined by the National Surgical Quality Improvement Program) were retrospectively abstracted from 587 women who underwent primary EOC staging between January 2, 2003, and December 29, 2008. Associations with receipt of PRBCT were evaluated using univariate logistic regression models. The associations between receipt of PRBCT and disease-free survival and overall survival were evaluated using multivariable Cox proportional hazards models and using propensity score matching and stratification, respectively.

RESULTS:

The rate of PRBCT was 77.0%. The mean ± SD units transfused was 4.1 ± 3.1 U. In the univariate analysis, receipt of PRBCT was significantly associated with older age, advanced stage (≥IIIA), undergoing splenectomy, higher surgical complexity, serous histologic diagnosis, greater estimated blood loss, longer operating time, the presence of residual disease, and lower preoperative albumin and hemoglobin. Perioperative packed red blood cell transfusion was not associated with an increased risk for recurrence or death, in an analysis adjusting for other risk factors in a multivariable model or in an analysis using propensity score matching or stratification to control for differences between the patients with and without PRBCT.

CONCLUSIONS:

Perioperative packed red blood cell transfusion does not seem to be directly associated with recurrence and death in EOC. However, lower preoperative hemoglobin was associated with a higher risk for recurrence. The need for PRBCT seems to be a stronger prognostic indicator than the receipt of PRBCT.

 

ABO blood group and risk of epithelial ovarian cancer within the Ovarian Cancer Association

open access

" There are two important limitations in the current study. First, controls in the UKG study were not selected at the same time as the cases and may not represent the population that gave rise to the cases. However, in a sensitivity analysis excluding the UKG study populations, the association with the A blood group was largely unchanged (Supplemental Table 4), suggesting that the UKG controls are not a large source of bias. Second, the current study had limited power for the analysis of subgroups, such as potential differences by histologic type, particularly for the less common types, such as clear cell. However, although not statistically significant within all groups, the results were largely consistent among the three most common histologic types (serous, endometrioid, and mucinous). Further, with 5,233 cases and 6,838 controls, this is the largest study of the association between ABO blood group and ovarian cancer to date, with 80% power to detect a relative risk of 1.17 for the AB blood group, indicating that we had adequate power to detect modest associations with even the rarest blood group. Further, this study improves upon previous studies by using appropriate control groups as well as genotype-derived blood groups, which are less likely to suffer from misclassification compared to self-reported blood type. Additionally, the use of genotype-derived blood groups allowed a more detailed investigation of diplotypes rather than the simple blood groups previously investigated."

In summary, our findings for blood group are consistent with previous findings of increased ovarian cancer risk with blood group A. Although potentially due to chance, the finding that this association is limited to the A1/O diplotype should be confirmed in additional studies. Given that the A blood type is associated with a modest increase in ovarian cancer risk, further research into the biological mechanisms linking blood group with carcinogenesis is warranted. 

Your Patient's Brain on Drugs -- Cancer Drugs: Cognitive Side Effects of Cancer Treatment

medscape

Peripheral Neuropathy in Ovarian Cancer - Dr Yi Pan

Peripheral Neuropathy in Ovarian Cancer - open access

Chemotherapy-induced peripheral neurotoxicity: A critical analysis

open access

Introduction

As a consequence of advances in cancer diagnosis and treatment, there are now an estimated 28 million cancer survivors worldwide.[1] As such, long-term quality of life is an increasingly important issue, with 67% of U.S. cancer patients surviving at 5 years. Addressing the long-term toxicities of cancer treatment is critical due to their potential impact on cancer survivorship.[2] Accordingly, there has been a gradual shift in focus toward postchemotherapy recovery and survivorship, with an awareness of the importance of the individual patient experience, patient-reported outcomes, and the long-term effects of treatment. Of particular importance is chemotherapy-induced peripheral neuropathy (CIPN), which can lead to permanent symptoms and disability in up to 40% of cancer survivors.[3] CIPN can be a significant disability following the treatment of many types of cancer, including breast, colorectal, testicular, and hematological malignancies, and have an impact on quality of life. As such, there is a critical need to understand pathophysiological mechanisms, optimize clinical assessment, and develop neuroprotective strategies to prevent neuropathy. This review will address the challenge of CIPN, highlighting treatment-related neuropathy caused by some of the most commonly used chemotherapeutic agents (such as taxanes, platinum compounds, vinca alkaloids, thalidomide, and bortezomib), and provide recommendations regarding assessment strategies, management, and follow-up.....


"The benefits of including direct patient evaluations include a more comprehensive and accurate assessment of CIPN, improved understanding of the impact of CIPN symptoms on the patient, and a better correlation of toxicity findings with functional outcomes."

 

Table 1. Chemotherapies Associated With Peripheral Neuropathy

Table 2. Assessment of CIPN Via Neuropathy Grading Scales

  

Table 3. Chemotherapy Dose and Duration as a Risk Factor for CIPN

Table 4. Current Clinical Trials in the Prevention and Treatment of CIPN

Table 5. CIPN Recommendations and Strategies 

Conclusions

CIPN remains a clinically significant and potentially serious side effect of cancer treatment, with increasing relevance to the millions of cancer survivors worldwide. The number of cancer survivors with disability due to CIPN is underreported, as the use of patient-reported outcomes and objective assessment tools typically reveal greater neurotoxicity than clinician assessment. Improved understanding concerning the pathophysiology underlying the development of CIPN and the diverse mechanisms across different chemotherapies seems crucial to the development of future neuroprotective strategies. Appropriate, standardized, and objective assessment tools combined with validated instruments that also document patient-reported symptoms will be necessary to identify the long-term impact of CIPN in cancer survivors. The dividend of improved cancer outcomes with advances in treatment may be compromised if we fail to develop approaches to minimize the chronic consequences of toxicities such as CIPN (Table 5).

 

The Retreatment of Carboplatin via High Dose Intraperitoneal Chemotherapy in Patients with a History of a Hypersensitivity Reaction

abstract

Purchase $35.95

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"A hypersensitivity reaction (HSR) attributed to platinum-based chemotherapy is a relatively common occurrence. Hyperthermic intraperitoneal chemotherapy (HIPEC) potentially facilitates the safe retreatment of platinum therapy following this complication. We describe three ovarian cancer patients who were successfully retreated with carboplatin via HIPEC following an HSR."

 

Plasma miRNAs as Diagnostic and Prognostic Biomarkers for Ovarian Cancer

open access (technical)

"Carbohydrate antigen-125 (CA-125) is the most frequently used biomarker for ovarian cancer detection [4], but it is only elevated in approximately 50% of stage I EOCs and 70%–90% of advanced cases [5]. Hence, there is a critical need for novel biomarkers that are more sensitive and specific for detecting EOC when used alone or in combination with CA-125. Recently, microRNAs (miRNAs), a family of small regulatory RNAs, emerged as possible plasma markers for human disease, including cancer, because of their relative stability in the circulation [6]."

Background

Most (70%) epithelial ovarian cancers (EOCs) are diagnosed late. Non-invasive biomarkers that facilitate disease detection and predict outcome are needed. The microRNAs (miRNAs) represent a new class of biomarkers. This study was to identify and validate plasma miRNAs as biomarkers in EOC.

Methodology/Principal Findings

We evaluated plasma samples of 360 EOC patients and 200 healthy controls from two institutions.

Conclusions/Significance

Our findings indicate that plasma miR-205 and let-7f are biomarkers for ovarian cancer detection that complement CA-125; let-7f may be predictive of ovarian cancer prognosis.