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Monday, August 29, 2016

Same Data; Different Interpretations - open access (ex. lung, ovarian, breast)

Same Data; Different Interpretations

Interpretation of oncology clinical trial data are not always straightforward or consistent. Similar trial results with disparate interventions may be interpreted differently by the oncology community. One of the main reasons for this discrepancy is the debate regarding what is the appropriate end point for demonstration of efficacy of cancer drugs. There is no doubt that overall survival (OS) is the best parameter to judge the utility of any intervention, and it is free from bias in ascertainment and measurement1; but for conditions with few treatment options and dire outcomes, the need for new agents is high and the oncology community sometimes settles on a surrogate end point that, in many cases, is progression-free survival (PFS).2 It is easy to understand why PFS is favored among the researchers: It occurs early and is not influenced by postprogression therapy. At the same time, it would make little sense to have an agent that reduces chances of dying of cancer but increases off-target deaths; hence, the need for verification of OS. Phase III trials that report on significant PFS benefits without OS prolongation become the apples of discord in the oncology community. In this commentary, we present three examples from lung, ovarian, and breast cancers and demonstrate how the oncology community interprets similar data differently. Finally, we take our best guess as to why this phenomenon happens. 

 Ovarian Cancer: Angiogenesis Inhibitors and Dose-Dense Chemotherapy

Several attempts have been made to build on the success of the platinum-taxane combination for treating advanced or metastatic ovarian cancer, but none have been met with irrefutable success. Of those various strategies, two are the most common and the most debated: dose-dense treatment schedule and addition of an angiogenesis inhibitor to the combination.
The feasibility and efficacy of a dose-dense schedule (weekly paclitaxel v every-3-week paclitaxel) was demonstrated in the Japanese Gynecologic Oncology Group (JGOG) 3016 trial, a study among 637 Japanese patients.10 This trial showed that weekly paclitaxel improved both PFS and OS. The OS advantage was not trivial; it was a sizable 38-month extension (100.5 months v 62.2 months; HR, 0.79; P = .039). However, the global oncology community adopted the addition of bevacizumab but has largely ignored the dose-dense paclitaxel schedule. Perhaps, the large benefit with weekly paclitaxel prompted clinicians to disbelief and wanting further confirmation; yet, it is hard to imagine clinicians believed a larger benefit would altogether vanish, rather than merely be attenuated........


We cannot also ignore the deep issues beyond clinical data that result in discrepancies in cancer care, such as politics, emotional overlay, lobbying, and advocacy of support groups. Although we explore three instances of discrepancies in the treatment of three similar cancer settings in this paper, many discrepancies exist in cancer care. When bevacizumab was revoked for breast cancer, support groups and patient advocates protested against the decision, but when 131I-tositumomab was withdrawn from marketing, it died silently. Thus, our attitudes toward cancer care are multifactorial. As oncologists, however, we should push for uniformity in the interpretation of clinical trial results and try to achieve as much consistency in our practice as possible. Consistency would be a virtue for cancer care.

Time to Diagnosis of Second Primary Cancers among Patients with Breast Cancer (BRCA)


Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of
Doctor of Philosophy Public Health

Many breast cancer diagnoses and second cancers are associated with BRCA gene
mutations. Early detection of cancer is necessary to improve health outcomes,
particularly with second cancers. Little is known about the influence of risk factors on time to diagnosis of second primary cancers after diagnosis with BRCA-related breast cancer. The purpose of this cohort study was to examine the risk of diagnosis of second primary cancers among women diagnosed with breast cancer after adjusting for BRCA status, age, and ethnicity. The study was guided by the empirical evidence supporting the mechanism of action in the mutation of BRCA leading to the development of cancer. Composite endpoint was used to define second primary cancer occurrences, and Kaplan- Meier survival curves were used to compare the median time-to-event among comparison groups and BRCA gene mutation status. Cox proportional hazards was used to examine the relationships between age at diagnosis, ethnicity, BRCA gene mutation status, and diagnosis of a second primary cancer. The overall median time to event for diagnosis of
second primary cancers was 14 years. The hazard ratios for BRCA2 = 1.47, White = 1.511, and American Indian/Hawaiian = 1.424 showed positive significant associations between BRCA2 mutation status and risk of diagnosis of second primary colorectal, endometrial, cervical, kidney, thyroid, and bladder cancers. Data on risk factors for development of second cancers would allow for identification of appropriate and timely screening procedures, determining the best course of action for prevention and treatment, and improving quality of life among breast cancer survivors.

Second cancers: For the purpose of this study, second cancer refers to any cancer
that a patient experienced after initial diagnosis with BRCA1- or BRCA2-related breast cancer.

(stigma/early integration) Perceptions of palliative care among patients with advanced cancer and their caregivers

 Grounded Theory is an inductive methodology. Although many call Grounded Theory a qualitative method, it is not. It is a general method. It is the systematic generation of theory from systematic research. It is a set of rigorous research procedures leading to the emergence of conceptual categories.


Background: Early palliative care is increasingly recommended but seldom practised. We sought to examine perceptions of palliative care among patients with advanced cancer and their caregivers.

Methods: After conducting a cluster randomized controlled trial of early palliative care versus standard care for patients with advanced cancer, we approached patients and their caregivers to participate in semistructured interviews seeking to assess, qualitatively, their attitudes and perceptions about palliative care. We used the grounded theory method for data collection and analysis. 

Results: A total of 48 patients (26 intervention, 22 control) and 23 caregivers (14 intervention, 9 control) completed interviews. Participants’ initial perceptions of palliative care in both trial arms were of death, hopelessness, dependency and end-of-life comfort care for inpatients. These perceptions provoked fear and avoidance, and often originated from interactions with health care professionals. During the trial, those in the intervention arm developed a broader concept of palliative care as “ongoing care” that improved their “quality of living” but still felt that the term itself carried a stigma. Participants in the intervention group emphasized the need for palliative care to be reframed and better explained by health care professionals. Participants in the control group generally considered it pointless to rename palliative care, but many in the intervention group stated emphatically that a different name was necessary in the early outpatient setting. 

Interpretation: There is a strong stigma attached to palliative care, which may persist even after positive experiences with an early palliative care intervention. Education of the public, patients and health care providers is paramount if early integration of palliative care is to be successful. 

related: (no abstract/requires paid subscription to view)

Treato: Ovarian Cancer - Risks, Symptoms and Leading Causes


Ovarian Cancer


Patient Assistance Programs "Culprits" of Rising Drug Prices

open access
PAP Series: Patient Assistance Programs "Culprits" of Rising Drug Prices 

....“If pharmaceutical companies want more credit for providing discounts for high-cost drugs, they are going to have to improve their relationships with patients, which could be achieved through further education about how much the companies invest in getting a new drug to market,” said Pamela Batzel, Treato's Senior Director of Consulting Services.

Treato is a big-data “social listening” company that uses natural language processing content-analysis algorithms to sift and initially analyze patients' online conversations about prescription drugs on social-media platforms like Facebook and Twitter, and dozens of patient discussion forums, mainly for drug company clients. Then human analysts follow up with content analyses of subsets of the captured conversations.....

Lipid profile of platelets and platelet-derived microparticles in ovarian cancer

open access


Ovarian cancer patients have a high risk of developing venous thrombosis. The membrane lipid bilayer of platelets and platelet-derived microparticles (PMP) provides a platform for assembly of coagulation proteins and generation of blood clots.


Our results support a procoagulant lipid profile of platelets in ovarian cancer patients that can play a role in the increased risk of venous thrombosis in these patients.....

General significance

As far as we are aware, our study is the first study on platelet lipidomics in ovarian cancer. The importance of our findings for the future studies are: 1) a similar change in lipid profile of platelets and PMP may be responsible for hypercoagulability in other cancers, and 2) plasma level of high-risk lipids for venous thrombosis may be useful biomarkers.

(maybe) Effects of cigarette smoke extracts on the progression and metastasis of human ovarian cancer cells

Effects of cigarette smoke extracts on the progression and metastasis of human ovarian cancer cells via regulating epithelial-mesenchymal transition


Cigarette smoke extracts (CSEs) increased ovarian cancer cell proliferation.
CSEs increased the migratory and invasive propensity of ovarian cancer cells.
CSEs regulated the protein expression of cell cycle, EMT, and metastasis related markers.
CS might pose a potential risk of ovarian cancer progression.

Cigarette smoke (CS) contains over 60 well-established carcinogens, and there are strong links between these carcinogens and smoking-induced cancers. In this study we investigated whether three types of cigarette smoke extracts (CSEs), 3R4F (standard cigarette), CSE1 and CSE2 (two commercial cigarettes), affect the proliferation, migration, and invasive activity of BG-1 human ovarian cancer cells. All three types of CSEs increased BG-1 cell proliferation at nicotine concentrations of 1.5 μM–2.1 μM in a cell viability assay. The protein expressions of cyclin D1 and cyclin E1 were increased, while p21 and p27 expression was decreased by Western blot assay. However, they did not show a consistent dose-dependent tendency. The protein expressions of Bax and p53, pro-apoptotic genes, were also decreased by CSEs. The expression of E-cadherin, an epithelial marker, was reduced in the treatment of CSEs while the expression of its reverse transition marker, N-cadherin, was slightly increased by CSEs containing 2.1 μM of nicotine, but a statistical significance was not observed. Epithelial-mesenchymal transition (EMT)-associated transcriptional factors, Snail and Slug, were also up-regulated by treatment with CSEs, indicating that CSEs can increase the EMT process in BG-1 ovarian cancer cells. In addition, CSEs increased the migratory and invasive propensity of cancer cells. These functional alterations were associated with changes in metastasis-related gene expression. Upon exposure to CSEs, the expression of MMP-9 and cathepsin D was increased. Taken together, we confirmed that CSEs increased the growth, migration, and invasion of human ovarian cancer cells by regulating cell cycle, apoptosis, EMT, and metastasis related cellular markers and signaling proteins. Based on the results, cigarette smokers of women might be at a higher risk of ovarian cancer than non-smokers.

Patient-Centered Care? Not for This Patient ("emotional torture: + comments)

Medpage Today

Fertility drugs and cancer: a guideline (ovarian + LMP, breast, endometrial)


 Methodological limitations in studying the association between the use of fertility drugs and cancer include the inherent increased risk of cancer in women who never conceive, the low incidence of most of these cancers, and that the age of diagnosis of cancer typically is many years after fertility drug use. Based on available data, there does not appear to be a meaningful increased risk of invasive ovarian cancer, breast cancer, or endometrial cancer following the use of fertility drugs. Several studies have shown a small increased risk of borderline ovarian tumors; however, there is insufficient consistent evidence that a particular fertility drug increases the risk of borderline ovarian tumors, and any absolute risk is small. Given the available literature, patients should be counseled that infertile women may be at an increased risk of invasive ovarian, endometrial, and breast cancer; however, use of fertility drugs does not appear to increase this risk.

(Lynch syndrome patients) Impact of Ureteroscopy Prior to Nephroureterectomy for Upper Tracturothelial Carcinoma on Oncologic Outcomes- Beyond the Abstract.

Blogger's Note: not specific to Lynch Syndrome but to surgical technique quandries

Impact of Ureteroscopy Prior to Nephroureterectomy for Upper Tracturothelial Carcinoma on Oncologic Outcomes- Beyond the Abstract

  Currently, there are conflicting data in literature assessing the association between URS and risk of intravesical recurrence, with most studies, like ours, consisting of small cohorts and adjusting for different covariates. A multi-institutional study would clarify whether a significant association between URS (ureteroscopy) and IR (intravesical tumor recurrences) till exists once more measured covariates are adjusted for. Results from such a study could aid treating physicians when deciding whether the benefits of pre−NU URS, including more accurate staging and possible endoscopic ablation, outweigh the increased risk of post−NU IR.

 Upper tract urothelial cell carcinoma (UTUC) is challenging to diagnose, stage, and manage. Historically, radical nephroureterectomy (NU) was performed for clinical suspicion of UTUC based primarily on imaging, with or without positive cytology. In the modern era, after the development of modern endoscopy techniques, many urologists will perform ureteroscopy (URS) prior to NU with diagnostic or therapeutic intent. The concern with this procedure is that it can disturb the tumor microenvironment and increase pyelovenous pressure with reports in the literature of disease progression following URS (1-4). Although these reports are anecdotal, it has led some urologists to advocate against upper tract instrumentation prior to NU. To address this concern, we compared the oncologic outcomes of patients with UTUC and no history of bladder cancer treated at our institution who were managed with and without URS prior to NU.....

Tackling cardiac toxicity of anticancer therapies

Science news

Currently, under- or over-diagnosis of cardiovascular disease sometimes results in failure to prevent adverse events or inappropriate interruption of a potentially life-saving anticancer treatment. "We need to be clear when it's a must to stop the treatment, when we should reduce the dose, or when we can continue with the therapy," said Professor Zamorano. "This position paper provides guidance in this area."

Laparoscopic Staging for Apparent Stage I Epithelial Ovarian Cancer: Analysis of the NCI Data Base (U.S.)



While advances in minimally invasive surgery have made laparoscopic staging technically feasible in stage I epithelial ovarian cancer, the practice remains controversial due to an absence of randomized trials and lack of high-quality observational studies demonstrating equivalent outcomes.


This study seeks to evaluate the association of laparoscopic staging with survival among women with clinical stage I epithelial ovarian cancer.


We used the National Cancer Data Base to identify all women who underwent surgical staging for clinical stage I epithelial ovarian cancer diagnosed from 2010-2012. The exposure of interest was planned surgical approach (laparoscopy versus laparotomy) and the primary outcome was overall survival. The primary analysis was based on intention-to-treat: all women whose procedures were initiated laparoscopically were categorized as having had a planned laparoscopic procedure regardless of subsequent conversion to laparotomy. We used propensity methods to match patients who underwent planned laparoscopic staging with similar patients who underwent planned laparotomy based on observed characteristics. We compared survival among the matched cohorts using the Kaplan-Meier method and Cox regression. We compared extent of lymphadenectomy using the Wilcoxon rank-sum test.


Among 4,798 eligible patients, 1,112 (23.2%) underwent procedures which were initiated laparoscopically, of which 190 (17%) were converted to laparotomy. Women who underwent planned laparoscopy were more frequently white, privately insured, from wealthier zip codes, received care in community cancer centers, and had smaller tumors that were more frequently of serous, and less often of mucinous histology than those who underwent staging via planned laparotomy. After propensity score matching, time to death did not differ between patients undergoing planned laparoscopic versus open staging (Hazard Ratio=0.77, 95%CI=0.54-1.09; p=0.13). Planned laparoscopic staging was associated with a slightly higher median lymph node count (14 versus 12, p=0.005). Planned laparoscopic staging was not associated with time to death after adjustment for receipt of adjuvant chemotherapy, histological type and grade, and pathologic stage (Hazard Ratio 0.82, 95% CI 0.57-1.16).


Surgical staging via planned laparoscopy versus laparotomy was not associated with worse survival in women with apparent stage I epithelial ovarian cancer.

A case report of Hepatoid Carcinoma of the Ovary with peritoneal metastases treated with cytoreductive surgery/HIPEC

open access:
A case report of Hepatoid Carcinoma of the Ovary with peritoneal metastases treated with cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy without systemic adjuvant therapy

The timeline of diagnosis, treatment, and follow up of our patient.


  • Hepatoid Ovarian Carcinoma (HCO) is rare diagnosis usually treated with debulking and adjuvant chemotherapy with a palliative intent.
  • Complete cytoreduction followed by HIPEC has been discussed as a potential curative option in absence of extraperitoneal disease.
  • The role of adjuvant chemotherapy is yet to be determined. In our case, a comparable disease-free survival was achieved without adjuvant therapies.

Cochrane crowd (become a citizen scientist - make a difference)

Cochrane crowd