Monday, June 11, 2012

NEJM: Improved Survival with MEK Inhibition in BRAF-Mutated Melanoma

The Trametinib trial for BRAF-Mutated Melanoma hits the NEJM this week.  The difference in OS despite crossover is remarkable for a chemo/targeted trial, and speaks to how much promise this treatment has in this subset of patients.


Improved Survival with MEK Inhibition in BRAF-Mutated Melanoma: New England Journal of Medicine,

Monday, June 4, 2012

RTOG released pelvic normal tissue atlas

In the Red Journal:

Normal tissue contouring guidelines are released for normal tissue contouring in this week red journal.  Extremely useful for those early in their career, and for defining a common criteria for OAR definition for clinical trial:

Link and Abstract:

Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas: Purpose: To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials.Methods and Materials: One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified.Results: The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa_R, Adnexa_L, Prostate, SeminalVesc, PenileBulb, Femur_R, and Femur_L. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed.Conclusions: Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.

Friday, June 1, 2012

11 year update on the German Rectal Cancer Trial

In the JCO this week:

The German Rectal trial is updated.  Again, local control benefit is confirmed out to long follow up, but this has not converted to an OS benefit.  Of course preventing local recurrence remains an important endpoint for this disease, and confirms what has been standard of care in the US since it's initial publication in the NEJM.

Link and Abstract

Preoperative Versus Postoperative Chemoradiotherapy for Locally Advanced Rectal Cancer: Results of the German CAO/ARO/AIO-94 Randomized Phase III Trial After a Median Follow-Up of 11 Years [Gastrointestinal Cancer]: Purpose
Preoperative chemoradiotherapy (CRT) has been established as standard treatment for locally advanced rectal cancer after first results of the CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society] trial, published in 2004, showed an improved local control rate. However, after a median follow-up of 46 months, no survival benefit could be shown. Here, we report long-term results with a median follow-up of 134 months.

Patients and Methods
A total of 823 patients with stage II to III rectal cancer were randomly assigned to preoperative CRT with fluorouracil (FU), total mesorectal excision surgery, and adjuvant FU chemotherapy, or the same schedule of CRT used postoperatively. The study was designed to have 80% power to detect a difference of 10% in 5-year overall survival as the primary end point. Secondary end points included the cumulative incidence of local and distant relapses and disease-free survival.

Of 799 eligible patients, 404 were randomly assigned to preoperative and 395 to postoperative CRT. According to intention-to-treat analysis, overall survival at 10 years was 59.6% in the preoperative arm and 59.9% in the postoperative arm (P = .85). The 10-year cumulative incidence of local relapse was 7.1% and 10.1% in the pre- and postoperative arms, respectively (P = .048). No significant differences were detected for 10-year cumulative incidence of distant metastases (29.8% and 29.6%; P = .9) and disease-free survival.

There is a persisting significant improvement of pre- versus postoperative CRT on local control; however, there was no effect on overall survival. Integrating more effective systemic treatment into the multimodal therapy has been adopted in the CAO/ARO/AIO-04 trial to possibly reduce distant metastases and improve survival.

NEJM: neoadjuvant CTRT for esophageal cancer

NEJM this week

Dutch investigators publish a randomized phase III trial looking at carbo-taxol+RT followed by surgery vs surgery alone for esophageal/GEJ cancers: they confirm a survival benefit to combined modality for both squams and adenos.  While prior studies did show a benefit (the Walsh trial and the CALGB trial) both had low numbers and other concerns (such as the low survival in the surgery alone arm of the Walsh trial).  This will hopefully close the book on surgery alone for all but the most early stages of disease.  There still remains the question of whether the RT is adding anything to this (there are the perioperative chemo alone trials from the UK which are also positive), but for now it seems the weight of data is clearly towards multimodal treatment for this aggressive disease.

Link to NEJM

Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer: New England Journal of Medicine, Volume 366, Issue 22, Page 2074-2084, May 2012.