Bevacizumab in ovarian cancer: Focus on clinical data and future perspectives

open access - pdf file

Conclusions: ..... As treatment options expand, the outlook for women with ovarian cancer is at last slowly but steadily improving.

 (blogger's note: questions still that need to be answered )eg. Nevertheless, there are no data available to answer the important question of whether bevacizumab can be used in combination with chemotherapy in both the front-line and recurrent setting in the same patient.

 Critical Reviews in Oncology/Hematology

 

Integrated genomic analysis of clear-cell ovarian cancer identifies PRKCI as a therapeutic target

Abstract 1102

 Clear-cell ovarian cancer (CCOC) is the third most common subtype of ovarian cancer. CCOC is more resistant to standard chemotherapy and has a poorer prognosis than serous and endometrioid histotypes. Through a comprehensive genomic approach, genes that are responsible for the aggressive behavior of CCOC were identified and their mechanism explored.

Genome-wide DNA copy number alterations were measured in 13 CCOC cell lines using high-resolution oligonucleotide array comparative genomic hybridization (Agilent 105k Human Genome CGH Microarray). .............. Thus, PKRCI can be considered as a potential novel CCOC-specific target; not only it inhibits malignant behavior of CCOC cells, but also induces the two major molecular pathways regulating cisplatin resistance. The results from the present study indicate that our comprehensive genomic analysis of CCOC allows identification of therapeutic targets responsible for the aggressive behavior specific of this ovarian cancer histotype and thus improve its therapeutic outcome.

Traditional Chinese medicine in the prevention and treatment of cancer and cancer metastasis (Review)

open access (see link - download pdf)

 Traditional Chinese medicine (TCM) has been a major part of healthcare in China, and has extensively affected medicine and healthcare in surrounding countries over a long period of time. In the fight against cancer, certain anticancer remedies using herbs or herbal formulas derived from TCM have been developed for the management of malignancies. Furthermore, there are clinical trials registered for the use of herbal remedies in cancer management. Herbal medicine has been used as part of combined therapies to reduce the side‑effects of chemotherapy, including bone marrow suppression, nausea and vomiting. Herbal remedies have also been used as chemopreventive therapies to treat precancerous conditions in order to reduce the incidence of cancer in high‑risk populations. Emerging evidence has revealed that herbal remedies can regulate the proliferation, apoptosis, adhesion and migration of cancer cells. In addition to this direct effect upon cancer cells, a number of herbal remedies have been identified to suppress angiogenesis and therefore reduce tumour growth. The inhibition of tumour growth may also be due to modifications of the host immune system by the herbal treatment. However, the precise mechanisms underlying the therapeutic effects of herbal remedies remain poorly understood and are yet to be fully elucidated. The present study aims to summarize the current literature and clinical trial results of herbal remedies for cancer treatment, with a particular focus on the recent findings and development of the Yangzheng Xiaoji capsule.

Intestinal Obstruction in Survivors of Childhood Cancer (abdominal/pelvic tumors)

abstract

 Intestinal Obstruction in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
 

Purpose For adult survivors of childhood cancer, knowledge about the long-term risk of intestinal obstruction from surgery, chemotherapy, and radiotherapy is limited. 

Methods Intestinal obstruction requiring surgery (IOS) occurring 5 or more years after cancer diagnosis was evaluated in 12,316 5-year survivors in the Childhood Cancer Survivor Study (2,002 with and 10,314 without abdominopelvic tumors) and 4,023 sibling participants. Cumulative incidence of IOS was calculated with second malignant neoplasm, late recurrence, and death as competing risks. Using piecewise exponential models, we assessed the associations of clinical and demographic factors with rate of IOS. 

Results Late IOS was reported by 165 survivors (median age at IOS, 19 years; range, 5 to 50 years; median time from diagnosis to IOS, 13 years) and 14 siblings. The cumulative incidence of late IOS at 35 years was 5.8% among survivors with abdominopelvic tumors, 1.0%  among those without abdominopelvic tumors, and 0.3%  among siblings. Among survivors, abdominopelvic tumor (adjusted rate ratio [ARR], 3.6 and abdominal/pelvic radiotherapy within 5 years of cancer diagnosis (ARR, 2.4 increased the rate of late IOS, adjusting for diagnosis year; sex; race/ethnicity; age at diagnosis; age during follow-up (as natural cubic spline); cancer type; and chemotherapy, radiotherapy, and surgery within 5 years of cancer diagnosis. Developing late IOS increased subsequent mortality among survivors (ARR, 1.8, adjusting for the same factors. 

Conclusion The long-term risk of IOS and its association with subsequent mortality underscore the need to promote awareness of this complication among patients and providers.

Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer

abstract

 OBJECTIVE:
OCEANS is a randomized, placebo (PL)-controlled, phase 3 trial evaluating the efficacy and safety of bevacizumab combined with gemcitabine+carboplatin (GC) for patients with platinum-sensitive recurrent ovarian cancer (ROC). The study met its primary endpoint, demonstrating improved progression-free survival with GC+bevacizumab compared with GC+PL. Herein, we describe results of final overall survival (OS) and updated safety.

METHODS:

Patients with recurrent platinum-sensitive ROC (recurring ≥6months after first-line platinum-based therapy) and measurable disease at baseline were randomized to receive GC+bevacizumab or GC+PL for 6-10 cycles; PL or bevacizumab was then continued until disease progression. In this updated analysis, a Cox proportional hazards model was used to compare OS between the 2 treatment arms.

RESULTS:

At the data cutoff date (July 19, 2013), 353 patients (72.9%) had died. Median follow-up for OS was 58.2 months in the experimental arm and 56.4months in the control arm. Consistent with interim analyses, median OS was comparable between arms (GC+bevacizumab: 33.6months; GC+PL: 32.9months; hazard ratio=0.95; log-rank p=0.65), and was consistent across all examined patient subgroups. The frequency and severity of adverse events were consistent with previous analyses; no new safety concerns were identified.

CONCLUSIONS:

Results from final OS analysis of the phase 3 OCEANS study showed no significant difference in OS for patients treated with GC+bevacizumab compared with GC+PL.

Screening adherence and cancer risk perceptions in colorectal cancer survivors with Lynch-like syndrome

abstract
 

BACKGROUND:

Cancer screening recommendations for patients with Lynch-like syndrome (LLS) are not well defined. We evaluated adherence to Lynch syndrome (LS) screening recommendations, cancer risk perceptions, and communication within the families among colorectal cancer (CRC) survivors with LLS.

METHODS:

Thirty-four participants with LLS completed a questionnaire about risk perception, adherence to LS screening recommendations, and communication with relatives. Clinical data were obtained from medical records.

RESULTS:

Most participants (76%) believed they should undergo colonoscopy every 1-2 years. Only 41% correctly interpreted their genetic tests as uninformative negative or as variant of unknown significance for LS. Less than half had had an upper GI endoscopy for screening purpose. Among female participants, 86% had been screened for endometrial cancer and 71% for ovarian cancer. Most participants had informed relatives about the CRC diagnosis and advised them to undergo CRC screening, but only 50% advised female relatives to be screened for endometrial cancer and only one-third advised relatives to have genetic counseling.

CONCLUSIONS:

Most CRC survivors with LLS follow the same cancer screening recommended for LS patients but do not understand the meaning of LLS. Greater care must be devoted to communicating the implications of non-diagnostic germline mutation testing among patients with LLS.

Cancer-Related Fatigue, NCCN Version 2.2015

NCCN Guidelines 2015
  
Defining Cancer-Related Fatigue

The panel defines CRF as a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning. Compared with the fatigue experienced by healthy individuals, CRF is more severe, more distressing, and less likely to be relieved by rest. In terms of the defining characteristics, the subjective sense of tiredness reported by the patient is important to note. As with pain, the clinician must rely on the description of fatigue and accompanying distress provided by the patient.....


Exercise interventions must be used with caution in patients with any of the following:

• Bone metastases
• Thrombocytopenia (low platelets)
• Anemia (low red blood cells)
• Fever or active infection
• Limitations secondary to metastasis or other comorbid illnesses

NCCN 2015 Genetic/Familial High-Risk Assessment: Colorectal

NCCN (references to non-polyposis/polyposis syndromes/Li-Fraumeni... + changes re: breast cancer also note: urothelial)

MSH1/2 + EPCAM mutation carriers

 There are data to suggest that aspirin may decrease the risk of colon cancer in LS; however, at this time the data are not sufficiently robust to make a recommendation for its standard use.

Extracolonic:

Endometrial and ovarian cancer:

Prophylactic hysterectomy and bilateral salpingo-oophorectomy (BSO) is a risk-reducing option that should be considered by women who have completed childbearing.

Patients must be aware that dysfunctional uterine bleeding warrants evaluation.

There is no clear evidence to support screening for endometrial cancer for LS. However, annual office endometrial sampling is an option.

While there may be circumstances where clinicians find screening helpful, data do not support routine ovarian screening for LS. Transvaginal ultrasound for ovarian and endometrial cancer has not been shown to be sufficiently sensitive or specific as to support a positive recommendation, but may be considered at the clinician’s discretion. Serum CA-125 is an additional ovarian screening test with caveats similar to transvaginal ultrasound.

Gastric and small bowel cancer: 

There is no clear evidence to support screening for gastric, duodenal, and small

bowel cancer for LS. Selected individuals or families or those of Asian descent

may consider EGD with extended duodenoscopy (to distal duodenum or into the jejunum) every 3–5 y beginning at age 30–35 y.

Urothelial

Consider annual urinalysis starting at 25–30 y.

 Central nervous system (CNS) cancer: 

Annual physical/neurologic examination starting at 25–30 y; no additional screening recommendations have been made.

Pancreatic cancer:  

Despite data indicating an increased risk for pancreatic cancer, no effective screening techniques have been identified; therefore, no screening recommendation is possible at this time.

Breast cancer: There have been suggestions that there is an increased risk for breast cancer in LS patients; however, there is not enough evidence to support increased screening above average-risk breast cancer screening recommendation

NCCN Guidelines Version 2.2015 Genetic/Familial High-Risk Assessment: Breast and Ovarian

NCCN Guidelines (93 pages also includes references to Cowden Syndrome/Lynch Syndrome/Li-Fraumeni....)

Oxaliplatin for the treatment of ovarian cancer, Expert Opinion on Investigational Drugs

abstract
 

Introduction: Oxaliplatin is an important drug in treatment of several solid tumors. Ovarian cancer (OC) is sensitive to chemotherapy and the overall response rate with primary therapy is about 75%. Unfortunately, 60 – 70% of patients experience recurrence requiring additional treatments and finally die of progressive disease within 5 years of the initial diagnosis. Currently, a platinum-based combination therapy is recommended in platinum-sensitive disease while a non-platinum single-agent therapy is preferred in platinum-resistant disease that is characterized by a low response rate.

Areas covered: In this article, the authors review the Phase II and Phase III studies of oxaliplatin as an OC therapy. Furthermore, the authors discuss the pharmacokinetic and pharmacodynamic features of oxaliplatin.

PARP inhibitors in the management of breast cancer: current data and future prospects

open access
 

Abstract

Poly(ADP-ribose) polymerases (PARP) are enzymes involved in DNA-damage repair. Inhibition of PARPs is a promising strategy for targeting cancers with defective DNA-damage repair, including BRCA1 and BRCA2 mutation-associated breast and ovarian cancers. Several PARP inhibitors are currently in trials in the adjuvant, neoadjuvant, and metastatic settings for the treatment of ovarian, BRCA-mutated breast, and other cancers. We herein review the development of PARP inhibitors and the basis for the excitement surrounding these agents, their use as single agents and in combinations, as well as their toxicities, mechanisms of acquired resistance, and companion diagnostics.

Pain typology and incident endometriosis

abstract
 

WIDER IMPLICATIONS OF THE FINDINGS:

Results of our research suggest that while women with endometriosis appear to have higher pelvic pain, particularly dyspareunia, dysmenorrhea, dyschezia and pain in the vaginal and abdominopelvic area than women with other gynecologic disorders or a normal pelvis, pelvic pain is commonly reported among women undergoing laparoscopy, even among women with no identified gynecologic pathology. Future research should explore causes of pelvic pain among women who seek out gynecologic care but with no apparent gynecologic pathology. Given our and other's research showing little correlation between pelvic pain and rASRM staging among women with endometriosis, further development and use of a classification system that can better predict outcomes for endometriosis patients with pelvic pain for both surgical and nonsurgical treatment is needed.

Hand-Assisted Robotic Surgery for Staging of Ovarian Cancer and Uterine Cancers With High Risk of Peritoneal Spread

abstract

 Hand-Assisted Robotic Surgery for Staging of Ovarian Cancer and Uterine Cancers With High Risk of Peritoneal Spread: A Retrospective Cohort Study

 OBJECTIVE: 

This study aimed to determine surgical outcomes related to hand-assisted robotic surgery (HARS) for staging of ovarian cancer and uterine cancers with high risk of peritoneal spread and compare them to laparotomy and standard robotic-assisted surgery.

Usefulness of Multigene Testing: Catching the Train That’s Left the Station

Commentary - open access (breast/ovarian genes)

Risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a 30-year semi-prospective analysis

abstract (UK)

 BRCA1 and BRCA2 mutation carriers have an increased risk of contralateral breast cancer after primary breast cancer. Risk reduction strategies are discussed after assessment of risk factors for developing contralateral breast cancer. We assessed potential risk factors that could be of use in clinical practice, including the novel use of single nucleotide polymorphisms (SNP) testing. 506 BRCA1 and 505 BRCA2 mutation carriers with a diagnosis of breast cancer were observed for up to 30 years. The risk of a contralateral breast cancer is approximately 2–3 % per year, remaining constant for at least 20 years. This was similar in both BRCA1 and BRCA2 carriers. Initial breast cancer before age 40-years was a significant risk factor, which was more pronounced in BRCA1 patients. The effect of risk-reducing oophorectomy on contralateral breast cancer risk may be overestimated because of bias. No significant association was found between overall breast cancer risk SNP score and contralateral breast cancer development. Young mutation carriers, particularly those with BRCA1 mutations, who develop breast cancer have a significantly higher risk of developing contralateral breast cancer, remaining constant for over 20 years. Contralateral risk-reducing mastectomy should be considered in this group, in particular as there is a survival benefit. Caution is advised when counselling women considering risk-reducing oophorectomy as, after accounting for statistical bias, the associated risk reduction was found to be non-significant, and potentially smaller than has been previously reported. SNP testing did not add any further discriminatory information when assessing contralateral breast cancer risk.