Friday, October 29, 2010

PET response in treatment of Esophageal cancer

JCO this week:

An interesting retrospective series from Wake Forest examines the potential role of PET in prediction and prognosis in Esophageal cancer. In this series, outcomes of patients treated with trimodality therapy (CT, RT, and surgery) did reasonably well regardless of PET response, but in the definitive CTRT group, PET-CR predicted a large difference in survival and local control. The question now is whether PET can be used to select patients that would benefit from surgery, after completing a course of CTRT, which could potentially spare up to a 1/3 of patient a potentially morbid intervention.

Link and Abstract:

Outcomes of Patients With Esophageal Cancer Staged With [18F]Fluorodeoxyglucose Positron Emission Tomography (FDG-PET): Can Postchemoradiotherapy FDG-PET Predict the Utility of Resection? [Gastrointestinal Cancer]: "Purpose
To determine whether [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) can delineate patients with esophageal cancer who may not benefit from esophagectomy after chemoradiotherapy.
Patients and Methods
We reviewed records of 163 patients with histologically confirmed stage I to IVA esophageal cancer receiving chemoradiotherapy with or without resection with curative intent. All patients received surgical evaluation. Initial and postchemoradiotherapy FDG-PET scans and prognostic/treatment variables were analyzed. FDG-PET complete response (PET-CR) after chemoradiotherapy was defined as standardized uptake value ≤ 3.
Eighty-eight patients received trimodality therapy and 75 received chemoradiotherapy. Surgery was deferred primarily due to medical inoperability or unresectable/metastatic disease after chemoradiotherapy. A total of 105 patients were evaluable for postchemoradiotherapy FDG-PET response. Thirty-one percent achieved a PET-CR. PET-CR predicted for improved outcomes for chemoradiotherapy (2-year overall survival, 71% v 11%, P < .01; 2-year freedom from local failure [LFF], 75% v 28%, P < .01), but not trimodality therapy. On multivariate analysis of patients treated with chemoradiotherapy, PET-CR is the strongest independent prognostic variable (survival hazard ratio [HR], 9.82, P < .01; LFF HR, 14.13, P < .01). PET-CR predicted for improved outcomes regardless of histology, although patients with adenocarcinoma achieved a PET-CR less often.
Patients treated with trimodality therapy found no benefit with PET-CR, likely because FDG-PET residual disease was resected. Definitive chemoradiotherapy patients achieving PET-CR had excellent outcomes equivalent to trimodality therapy despite poorer baseline characteristics. Patients who achieve a PET-CR may not benefit from added resection given their excellent outcomes without resection. These results should be validated in a prospective trial of FDG-PET–directed therapy for esophageal cancer.

Tuesday, October 12, 2010

JCO: Gem+RT vs Gem alone in Pancreatic CA


Pancreatic cancer continues to be a difficult tumor to treat, where even the largest recent advances (EGRF inhibition, Gemcitabine) provide very modest benefit at best. Gemcitabine + RT was a subject of some excitement due to the radiosensitizing properties of the drug, but unfortunately in many centers it was found to also sensitize to normal tissue as well. Thus the US approach has been Gem alone, and RT + 5FU or capecitabine if used at all.

The study at hand is at once great in terms of concept by looking at Gem alone vs Gem concurrently with RT , but unfortunately limited by it's scope. As a randomized phase II, little can be concluded, asside from the fact that the toxicities as less than otherwise expected in the concurrent arm. There is not however evidence of a large therapeutic benefit with the approach, thus I feel that, as before, this is a disease in desperate need of a breakthrough.

Link and Abstract

Adjuvant Gemcitabine Alone Versus Gemcitabine-Based Chemoradiotherapy After Curative Resection for Pancreatic Cancer: A Randomized EORTC-40013-22012/FFCD-9203/GERCOR Phase II Study [Gastrointestinal Cancer]: "Purpose

The role of adjuvant chemoradiotherapy (CRT) in resectable pancreatic cancer is still debated. This randomized phase II intergroup study explores the feasibility and tolerability of a gemcitabine-based CRT regimen after R0 resection of pancreatic head cancer.

Patients and Methods

Within 8 weeks after surgery, patients were randomly assigned to receive either four cycles of gemcitabine (control arm) or gemcitabine for two cycles followed by weekly gemcitabine with concurrent radiation (50.4 Gy; CRT arm). The primary objective was to exclude a < 60% treatment completion and a > 40% rate of grade 4 hematologic or GI toxicity in the CRT arm with type I and II errors of 10%. Secondary end points were late toxicity, disease-free survival (DFS), and overall survival (OS).


Between September 2004 and January 2007, 90 patients were randomly assigned (45:45). Patient characteristics were similar in both arms. Treatment was completed per protocol by 86.7% and 73.3% (80% CI, 63.1% to 81.9%; 95% CI, 58.1% to 85.4%) in the control and CRT arms, respectively, and grade 4 toxicity was 0% and 4.7% (two of 43; 80% CI, 1.2% to 11.9%), respectively. In the CRT arm, three patients experienced grade 3–related late toxicity. Median DFS was 12 months in the CRT arm and 11 months in the control arm. Median OS was 24 months in both arms. First local recurrence was less frequent in the CRT arm (11% v 24%).


Adjuvant gemcitabine-based CRT is feasible, well-tolerated, and not deleterious; adding this treatment to full-dose adjuvant gemcitabine after resection of pancreatic cancer should be evaluated in a phase III trial.



Lancet Oncology -

An interesting review article on angiosarcoma in the Lancet Oncology this week: these difficult tumors often involve the radiation oncologist, either as a long term complication of prior therapy (classically breast radiation), or as treatment.


[Review] Angiosarcoma: "Angiosarcomas are rare soft-tissue sarcomas of endothelial cell origin that have a poor prognosis. They can arise anywhere in the body, most commonly presenting as cutaneous disease in elderly white men, involving the head and neck and particularly the scalp. They can be caused by therapeutic radiation or chronic lymphoedema and hence secondary breast angiosarcomas are an important subgroup. Recent work has sought to establish the molecular biology of angiosarcomas and identify specific targets for treatment."

NSABP B-32 - Sentinel Node Study published for OS

In the Lancet Oncology,

Though already common practice, the NSABP B-32 trial randomizing breast cancer patients to sentinel lymph node mapping vs a full axillary dissection is published revealing no difference in any clinical endpoint. This is good news as it already has become standard practice in most US centers. Another thing to keep in mind about this is that there is a 5-15% false negative rate of the procedure, which has clearly not translated into a meaningful difference in outcomes in this trial.


[Articles] Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial: "Overall survival, disease-free survival, and regional control were statistically equivalent between groups. When the SLN is negative, SLN surgery alone with no further ALND is an appropriate, safe, and effective therapy for breast cancer patients with clinically negative lymph nodes."

Friday, October 1, 2010

Cabazitaxel for Prostate CA


Interesting phase III trial reported in Lancet this week: the study population was of patient with castrate resistant, metastatic prostate cancer, progressing after docetaxel. They were randomized to mitoxantrone vs. a novel taxane cabazitaxel. Toxicity was higher with cabazitaxel, but there was an improvement in both progression free and overall survival. As rad oncs are occaisionally the primary oncologists that prostate cancer patients see, this is a signficant advance worthy of our notice.


[Articles] Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial: "Prostate cancer is the second most common cause of cancer death in men in the USA and the third most common cause of death in developed countries. For patients with metastatic prostate cancer, androgen deprivation therapy improves symptoms, but patients invariably develop progressive disease. On the basis of an improvement in survival compared with mitoxantrone plus prednisone in patients with metastatic castration-resistant prostate cancer, docetaxel in combination with prednisone is standard first-line chemotherapy in this setting. No treatment has been approved by the US Food and Drug Administration, however, for patients whose disease progresses after docetaxel treatment. Mitoxantrone is often administered because of its favourable effects on quality-of-life outcomes. However, no intervention improves survival in this disease setting."