Cancer Explained – The Role of Cell Death « Dr. Robert A. Nagourney – Rational Therapeutics – Blog

Blogger's Note: includes a commentary from (appreciative often-poster to this blog) Gregory Pawelski

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Cancer Explained – The Role of Cell Death « Dr. Robert A. Nagourney – Rational Therapeutics – Blog

open access: European cancer mortality predictions for the year 2013

Blogger's Note: this publication is now open access (previously blog posting as an abstract); not included were specific references to ovarian cancer

European cancer mortality predictions for the year 2013

High Death Risk Tied to mTOR Drugs in Cancer ( rapamycin)

Blogger's Note: clinical trials in renal (kidney) and other cancers

High Death Risk Tied to mTOR Drugs in Cancer

Action Points

• This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Fatal adverse events occurred more than twice as often in cancer patients treated with mammalian target of rapamycin (mTOR) inhibitors compared with control therapies.
• Point out that the most commonly identified cause of death was sepsis/infection.

repost: open access: Clinicopathological Features and Management of Cancers in Lynch Syndrome

Clinicopathological Features and Management of Cancers in Lynch Syndrome

Ovarian angiosarcoma: Extended survival following optimal cytoreductive surgery and adjuvant chemotherapy

ScienceDirect.com - Gynecologic Oncology Case Reports - Ovarian angiosarcoma: Extended survival following optimal cytoreductive surgery and adjuvant chemotherapy

Gynecologic Oncology Case Reports - Destructive T10 vertebral lesion leads to diagnosis of metastatic ovarian cancer

ScienceDirect.com - Gynecologic Oncology Case Reports - Destructive T10 vertebral lesion leads to diagnosis of metastatic ovarian cancer

Does Enrollment in Cancer Trials Improve Survival?

Blogger's Note: to fully appreciate the conclusions the full paper ($$$)/discussion is needed

ScienceDirect.com - Journal of the American College of Surgeons - Does Enrollment in Cancer Trials Improve Survival?

 Purchase $31.50

Abstract

Background

Stakeholders derive many benefits from cancer clinical trials, including guidance for future oncologic treatment decisions. However, whether enrollment in cancer trials also improves patient survival independently of trial outcomes remains under investigated. We hypothesized that cancer trial enrollment is not associated with patient survival outcomes.

Bidirectional modulation of endogenous EpCAM expression to unravel its function in ovarian cancer

 Blogger's Note: the EpCAM gene is also tested in Lynch Syndrome patients/families

Abstract:

Background:

The epithelial cell adhesion molecule (EpCAM) is overexpressed on most carcinomas. Dependent on the tumour type, its overexpression is either associated with improved or worse patient survival. For ovarian cancer, however, the role of EpCAM remains unclear.

Conclusion:

The bidirectional ATF-based approach is uniquely suited to study cell-type-specific biological effects of EpCAM expression. Using this approach, the oncogenic function of EpCAM in breast cancer was confirmed. Despite its value as a diagnostic marker and for immunotherapy, EpCAM does not seem to represent a therapeutic target for gene expression silencing in ovarian cancer.

open access: Socio-demographic inequalities in stage of cancer diagnosis: evidence from patients with female breast, lung, colon, rectal, prostate, renal, bladder, melanoma, ovarian and endometrial cancer

Socio-demographic inequalities in stage of cancer diagnosis: evidence from patients with female breast, lung, colon, rectal, prostate, renal, bladder, melanoma, ovarian and endometrial cancer

Background
Understanding socio-demographic inequalities in stage at diagnosis can inform priorities for cancer control.

".....The absence of socio-demographic variation in stage at diagnosis of three cancers (colon, rectal and ovarian cancer) should not be interpreted as an indication that patient awareness interventions for those three cancers are not justified. Such interventions are currently being implemented for colorectal cancer [37], while evidence increasingly supports their consideration for ovarian cancer [38]. The findings need to be interpreted in relation to their temporal context (2006–2010). Evidence from breast cancer and melanoma which both benefited from long-standing awareness campaigns indicates that when such interventions are effective [39], they tend to also generate health inequalities (younger and more affluent people typically being able to benefit more so than older and less affluent people) [40]. Avoiding potential inequality that can be generated by future effective patient awareness campaigns about colorectal and ovarian cancer presents a challenge.

In conclusion, for most cancers, there are appreciable socio-demographic inequalities in stage at diagnosis, and this realisation can help motivate and support targeting of interventions on patients at higher risk"

A multicenter, randomized trial of flat dosing versus intrapatient dose escalation of single-agent carboplatin as first-line chemotherapy for advanced ovarian cancer: an SGCTG (SCOTROC 4) and ANZGOG study on behalf of GCIG

A multicenter, randomized trial of flat dosing versus intrapatient dose escalation of single-agent carboplatin as first-line chemotherapy for advanced ovarian cancer: an SGCTG (SCOTROC 4) and ANZGOG study on behalf of GCIG

Background 

The aim of the study is to demonstrate that intrapatient dose escalation of carboplatin would improve the outcome in ovarian cancer compared with flat dosing. 

Patients and methods 

Patients with untreated stage IC-IV ovarian cancer received six cycles of carboplatin area under the curve 6 (AUC 6) 3 weekly either with no dose modification except for toxicity (Arm A) or with dose escalations in cycles 2–6 based on nadir neutrophil and platelet counts (Arm B). The primary end-point was progression-free survival (PFS).

Conclusions
Intrapatient dose escalation of carboplatin based on nadir blood counts is feasible and safe. However, it provided no improvement in PFS or OS compared with flat dosing. Baseline neutrophils over-ride nadir counts in prognostic significance. These data may have wider implications particularly in respect of the management of chemotherapy-induced neutropenia. 

If nothing happens, is everything alright? Assessing validity of adverse effects data - webinar/Cochrane

Early 2013 Webinar Series | Canadian Cochrane Centre

Wednesday, 27 February 2013, 12-1PM EST (Toronto); conducted in English

• Systematic reviews of adverse effects are often hampered by findings of sparse data, or zero events. Results are frequently interpreted based on statements such as “no significant harm was found” or “the intervention was safe and well-tolerated.” Join Yoon K Loke, Co-Convenor of the Cochrane Adverse Effects Methods Group, for this webinar, which will focus on pitfalls in evaluating adverse effects data.  Both authors and referees of systematic reviews are welcome.

open access: Antimicrobial Prophylaxis and Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: ASCO

 Blogger's Note: although this is one of a number of practice guidelines on this issue, it is worth reading; it also addresses disparities in access

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Antimicrobial Prophylaxis and Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology Clinical Practice Guideline

Purpose
To provide guidelines on antimicrobial prophylaxis for adult neutropenic oncology outpatients and on selection and treatment as outpatients of those with fever and neutropenia

Victory for gene patent firm in Australian court - health - 15 February 2013 - New Scientist

Victory for gene patent firm in Australian court - health - 15 February 2013 - New Scientist

"Your genes are the same, whether in a test tube or inside your body. But the very act of removing them makes them a patentable invention, according to Australia's Federal Court."

"The ruling comes just two months before the US Supreme Court will hear an appeal over a very similar case between Myriad and the American Civil Liberties Union, which was awarded to Myriad in a lower court."

open access: Phase I dose-escalation study of afatinib, an ErbB family blocker, plus docetaxel in patients with advanced cancer, Future Oncology, Future Medicine

 Blogger's Note: of the 31 patients included in this study 14 were ovarian cancer patients

Phase I dose-escalation study of afatinib, an ErbB family blocker, plus docetaxel in patients with advanced cancer, Future Oncology, Future Medicine

Aims:
To determine the maximum tolerated dose (MTD), safety and anti-tumor activity of afatinib combined with docetaxel in advanced cancer. 

Patient demographics
Thirty-one patients were treated and included in all analyses. Baseline demographics are presented in Table 1. The patient population was heavily pretreated; 64.5% had received ≥3 lines of prior chemotherapy and 54.8% had received prior radiotherapy.

Anti-tumor activity

No objective responses were observed during the study. The best overall response was stable disease, which was achieved in 14 (45.2%) of all treated patients. The median duration of stable disease was 82.5 days. Disease stabilization was observed in four of the six patients treated at the MTD. Seven patients completed four treatment cycles.......

Conclusion & future perspective

This study defined an MTD of afatinib of 20 mg/day when given in combination with 75 mg/m² docetaxel on a 3-weekly dosing schedule, involving administration of docetaxel on day 1, followed by daily afatinib on days 2–21. The safety profile of this regimen was manageable. The inability to escalate afatinib to doses achieved in other trials, despite the lack of PK interactions, did not permit recommendation of a possible Phase II dose. A new dose-finding study in a less-heavily pretreated patient population, where the use of GM-CSF is recommended, is currently ongoing

Health News - Cured of cancer but in poor health

Health News - Cured of cancer but in poor health

open access: Radiation therapy for epithelial ovarian cancer brain metastases: clinical outcomes and predictors of survival

Radiation therapy for epithelial ovarian cancerbrain metastases: clinical outcomes and predictors of survival


 Clinical characteristics

Patient characteristics at the time of initial BM diagnosis are listed in Table 1. Median age at diagnosis of EOC was 56.1 years (range, 31.2-79.0). Stage distribution [20] at original diagnosis of EOC was 3 patients with stage I (5%), 4 with stage II (6.7%), 40 with stage III
(66.7%), and 13 with stage IV (21.7%). Histologic grade at diagnosis was 2 patients with grade 1 (3%), 7 with grade 2 (12%), 49 with grade 3 (82%), and 2 unknown (3%). Tumor histology was distributed as follows: 42 (70%) papillary serous, 8 (13%) endometrioid, 3 (5%) adenocarcinoma not otherwise specified, 2 (3%) mixed carcinoma, and 1 each of mixed
adenocarcinoma, clear cell carcinoma, mucinous adenocarcinoma, small cell carcinoma, and cystic ovarian carcinoma.
  
Conclusions

Based on our results, RT appears to be an effective treatment modality for brain metastases from EOC and should be routinely offered. Karnofsky performance status less than 70, four or more BM, LMD, and uncontrolled primary tumor predict for worse survival after RT for
EOC BM. Whether RT is superior to surgery or chemotherapy for EOC BM remains to be seen in a larger cohort.

open access: When evidence and common sense collide - Resident hours and systems of care

When evidence and common sense collide

Rebuttal: Is the elimination of 24-hour resident call a good idea? NO

Rebuttal: Is the elimination of 24-hour resident call a good idea?

Rebuttal: Is the elimination of 24-hour resident call a good idea? YES

Rebuttal: Is the elimination of 24-hour resident call a good idea?

No increased cancer risk after IVF: study - Reuters

Blood clotting activation analysis for preoperative differentiation of benign versus malignant ovarian masses

Abstract

Preoperative evaluation of patients presenting with ovarian masses is challenging, partly due to shortcomings with the commonly used marker, CA-125. Ovarian cancer is associated with systemic coagulation activation. Measurement of D-dimer, serum tissue factor (TF), and the coagulation process as a whole are considered candidates for improving discrimination between benign and malignant ovarian masses. We therefore sought to identify possible benefits by analyzing preoperative coagulation status in conjunction with CA-125 in patients with ovarian masses.

Usefulness of Intraoperative Imprint Cytology in Ovarian Germ Cell Tumors

Abstract

Objective: 
This study retrospectively investigated the usefulness of intraoperative diagnosis based on imprint cytology and frozen sections for ovarian germ cell tumor.

Diagnosis and treatment of the epithelial ovarian cancer at the West African Cancer Center of Dakar.

Diagnosis and treatment of the epithelial ovarian cancer at the West African Cancer Center of Dakar.:

Abstract

Introduction.
Epithelial ovarian cancer are the most frequent of ovarian cancer, their prognosis is very bad. The aim of this study is to describe the diagnosis, the treatment and to assess the survival rate of the patients.

Methods. It was a retrospective study realized at the Cancer Institute of Dakar from December 2000 to January 2007. We have collected 117 patients with epithelial ovarian cancer. The mean age was 49 years. Patients were comprised: 22 stage I, 32 stage II, 35 stage III and 26 stage IV. Primary surgery was performed to 34 patients and the other patients were treated with chemotherapy and surgery. The survival rate was assessed by Kaplan-Meier method and the Logrank test had allowed to compare the survival among age and optimal surgery.

Results. Optimal surgery R0 was done in 20 cases and surgical resection R2 was performed in 45 cases. Pathological exam had found 65 serous cystadenocarcinoma, 28 mucinous cystadenocarcinoma and 21 endometrioid cystadenocarcinoma, one malignant tumor of Brenner. Overall survival at five years was 13.3%. The survival among optimal surgery was 16.3 and 2.3% for suboptimal surgery. There was no significant difference of the survival among patients who were less than 40 years old (P = 0.334).

Conclusion.
Prognosis of epithelial ovarian cancer is worse in Senegal as like as in the world. To improve the survival of our patients, we must detect the early diagnosis of these tumors and to introduce the neoadjuvant chemotherapy before optimal surgery.

open access: BJC - Functional imaging: what evidence is there for its utility in clinical trials of targeted therapies?

Functional imaging: what evidence is there for its utility in clinical trials of targeted therapies?

"An increasing knowledge about the major pathways dysregulated in cancer has resulted in a large array of targeted pathway inhibitors submitted for phase I trials. Recent figures suggest that <10% of new molecules reach the market primarily because of a lack of demonstrable clinical activity (Kola and Landis, 2004). Other contributing factors include lack of appropriate quantitative imaging methods to guide both preclinical and clinical development. The standard imaging assessment of tumour response relies on size measurements, which, with predominantly cytostatic targeted agents, may not reflect the drug effect. The wide therapeutic index of targeted agents, non-linear relationship between dose and effect and non-mechanism related toxicity may require definition of an optimal biological dose rather than a maximal tolerated dose (MTD). Also, many of these agents may prove to be more effective in combination therapy either with synergistic targeted agents or with chemotherapy and the minimum biologically active dose needs also to be determined. Moreover, because targeted agents are approved for cancer treatment largely based on marginal benefits shown in clinical trials, it means that a large percentage of patients may merely suffer toxicity without therapeutic benefit........

Trials - Sentinel node in ovarian cancer: study protocol for a phase 1 study

Trials | Abstract | Sentinel node in ovarian cancer: study protocol for a phase 1 study

Background

The concept of sentinel lymph node surgery is to determine whether the cancer has spread to the very first lymph node or sentinel node. If the sentinel node does not contain cancer, then there is a high likelihood that the cancer has not spread to other lymph nodes. The sentinel node technique has been proven to be effective in different types of cancer. In this study we want to determine whether a sentinel node procedure in patients with ovarian cancer is feasible when the tracers are injected into the ovarian ligaments.

Methods

Patients with a high likelihood of having an ovarian malignancy in whom a median laparotomy and a frozen section analysis is planned and patients with endometrial cancer in whom a staging laparotomy is planned will be included.

Before starting the surgical staging procedure, blue dye and radioactive colloid will be injected into the ligamentum ovarii proprium and the ligamentum infundibulo-pelvicum. In the analysis we calculate the percentage of patients in whom it is feasible to identify sentinel nodes. Other study parameters are the anatomical localization of the sentinel node(s) and the incidence of false negative lymph nodes. 

Trial registration: Approval number: NL40323.068.12

Name: Medical Ethical Committee Maastricht University Hospital, University of Maastricht (Netherlands)

Affiliation: Maastricht University Hospital

Board Chair Name: Medisch Ethische Commissie azM/UM

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