Marital Status and Overall Survival in Patients with Resectable Pancreatic Cancer: Results of an Ancillary Analysis of NRG Oncology/RTOG 9704.

BACKGROUND: Several registry-based analyses suggested a survival advantage for married versus single patients with pancreatic cancer. The mechanisms underlying the association of marital status and survival are likely multiple and complex and, therefore, may be obscured in analyses generated from large population-based databases. The goal of this research was to characterize this potential association of marital status with outcomes in patients with resected pancreatic cancer who underwent combined modality adjuvant therapy on a prospective clinical trial. MATERIALS AND METHODS: This is an ancillary analysis of 367 patients with known marital status treated on NRG Oncology/RTOG 97-04. Survival analysis was performed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model. RESULTS: Of 367 patients, 271 (74%) were married or partnered and 96 (26%) were single. Married or partnered patients were more likely to be male. There was no association between marital status and overall survival (OS) or disease-free survival (DFS) on univariate (hazard ratio [HR], 1.09 and 1.01, respectively) or multivariate analyses (HR, 1.05 and 0.98, respectively). Married or partnered male patients did not have improved survival compared with female or single patients. CONCLUSION: Ancillary analysis of data from NRG Oncology/RTOG 97-04 demonstrated no association between marital and/or partner status and OS or DFS in patients with resected pancreatic cancer who received adjuvant postoperative chemotherapy followed by concurrent external beam radiation therapy and chemotherapy. Clinical trial identification number. NCT00003216. IMPLICATIONS FOR PRACTICE: Several population-based studies have shown an epidemiological link between marital status and survival in patients with pancreatic cancer. A better understanding of this association could offer an opportunity to improve outcomes through psychosocial interventions designed to mitigate the negative effects of not being married. Based on the results of this analysis, patients who have undergone a resection and are receiving adjuvant therapy on a clinical trial are unlikely to benefit from such interventions. Further efforts to study the association between marital status and survival should be focused on less selected subgroups of patients with pancreatic cancer.

Treatment interruption and discontinuation in radiotherapy for rectal cancer.

Radiotherapy with chemotherapy for rectal cancer reduces local recurrence risk. Of 113 patients (59 male, 54 female) undergoing treatment at New York Presbyterian Hospital, 1998-2007, 6 discontinued radiotherapy; all were female. Females were also more likely to have a treatment interruption (35% vs 12%, p = .004). Other factors associated with treatment interruption included adjuvant versus neoadjuvant therapy (OR 14.08, 95%CI 1.55-127.87), use of capecitabine versus 5-fluorouracil (OR 75.90, 95%CI 3.33->999), and development of any adverse event (OR 20.66, 95%CI 1.76-242.12). While radiotherapy discontinuation was uncommon in our cohort, for unknown reasons, females were more likely to discontinue or interrupt treatment.

HIV positivity but not HPV/p16 status is associated with higher recurrence rate in anal cancer.

AIM: Human papillomavirus (HPV) is a pathogenic factor of squamous cell carcinoma in various mucosal locations, including anal carcinoma (ACA). It is also known that patients positive for HIV are at high risk of ACA. The goal of this study was to examine clinical outcome in ACA in relation to HPV/p16 positivity, histologic tumor differentiation, and HIV status. Patients with oropharyngeal cancers that are positive for HPV and show overexpression of p16 as well as having non-keratinizing/basaloid histology have been reported to have better outcomes following chemoradiation (CRT). However, such relationships in ACA remain unknown. METHODS: Forty-two patients with SCC of the anus treated with CRT between 1997 and 2009 were identified. The tumors were subclassified as either non-keratinizing (including basaloid) or keratinizing categories. HPV testing was performed using SPF10-PCR, and all cases were immunostained for p16. RESULTS: There were 23 men and 19 women; 43% of men and 11% of women were HIV-positive (p = 0.04). Fifty-five percent of patients had local disease (stages I and II) and 41% were stages III and IV, with 4% stage unknown. All tumors were positive for high-oncogenic risk HPVs, and all were positive with p16 immunostain. Sixty-four percent of tumors were non-keratinizing/basaloid and 36 % were keratinizing. The keratinizing tumors were more common in HIV-positive patients (67%), whereas non-keratinizing/basaloid tumors were more common in HIV-negative patients (77%) (p = 0.008). Thirty-one percent of patients had recurrence of disease, including 50% HIV-positive patients and 23% HIV-negative patients (p = 0.09). There was no difference in the recurrence rate between non-keratinizing and keratinizing tumor subtypes (p = 0.80). The 24-month recurrence-free survival for the cohort was 66% (95% CI = 46%, 81%), with HIV-positive patients having worse recurrence-free survival compared to HIV-negative patients (HR = 2.85, 95% CI = 0.95, 8.53; p = 0.06). CONCLUSION: The regional and distant failure rate was not related to HPV/p16 positivity or histologic differentiation of ACA; however, HIV positivity appeared to be associated with a higher recurrence rate and worse recurrence-free survival.

Stereotactic radiosurgery plays a critical role in enhancing long-term survival in a patient with pancreatic cancer metastatic to the brain.

BACKGROUND: Pancreatic cancer is an aggressive disease which metastasizes readily. The presence of brain metastases from pancreatic cancer is rare and it carries a poor prognosis. Our approach to treating these lesions stresses extensive use of stereotactic radiosurgery (SRS), whereas other reports focus on surgical resection. CASE REPORT: Information regarding the patient's clinical history was extracted from a retrospective review of the medical records and imaging studies. The patient survived seven years after his primary diagnosis of pancreatic cancer, and 36 months after diagnosis of metastatic disease to the brain. In addition to surgical resection and the use of multiple chemotherapeutic agents, the patient received six separate radiosurgery treatments. CONCLUSION: We present a case of brain metastasis from pancreatic cancer that is remarkable for an unusually long survivorship and discuss the utility of SRS along with a multimodality treatment approach for dealing with these cases.

Demographic disparities in patterns of care and survival outcomes for patients with resected gastric adenocarcinoma.

BACKGROUND: Several reports showed incomplete adoption of adjuvant radiotherapy (RT) for resectable gastric cancer since the publication of Intergroup 0116 trial results. The aims of this study were to identify demographic factors associated with omission of adjuvant RT and assess the impact of this omission on survival. METHODS: SEER database was queried for cases of resected gastric cancer. Multivariate analyses with logistic and Cox regressions were used to examine (a) likelihood of receiving adjuvant RT for different patient and county demographics and (b) effect of demographics on survival outcomes. RESULTS: A total of 7,348 patients met the study criteria. Adjuvant RT was used in 33.1% of cases diagnosed in 1998-2001 and in 45.3% of cases in 2002-2007 (P < 0.001). Controlling for independent covariates, African Americans were 8.9% less likely to receive adjuvant RT than Caucasians or Asians (P < 0.001). Correspondingly, overall survival rates were significantly lower for African Americans than other races (HR = 1.38, P < 0.001). Furthermore, both the likelihood of receiving RT and the survival rates were significantly affected by county demographics: percent of population without high school education, percent of households below the poverty line, and median household income. Survival rates were highest among Asians, but this finding did not reflect more frequent use of RT. CONCLUSIONS: Race and socioeconomic factors are significant predictors of treatment and survival outcomes for patients with resectable gastric cancer. IMPACT: The findings of this and similar studies may aide the medical community in designing more effective strategies to ameliorate the standards of care nationwide.

Increasing incidence of rectal cancer in patients aged younger than 40 years: an analysis of the surveillance, epidemiology, and end results database.

BACKGROUND: The incidence of rectal cancer in the United States in young patients is considered to be low. Underestimating this incidence may result in a failure to diagnose younger patients with rectal cancer in a timely manner. METHODS: The authors conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) cancer registry data. A total of 7661 patients with colon, rectal, and rectosigmoid cancer who were diagnosed at age <40 years were identified between 1973 and 2005. The change in incidence over time for colon and rectal/rectosigmoid cancer was calculated and the annual percent change for anatomic subsites of colorectal cancer compared. RESULTS: SEER data demonstrated an increase in the incidence of rectal cancer without any increase in colon cancer (annual percent change of 2.6% vs -0.2%). The difference was statistically significant and extended to rectosigmoid cancer, but not cancer of the sigmoid colon or descending colon (annual percent change of 2.2% vs 0.4% and -2.8%, respectively). Joinpoint analysis of the slope of the curve of rectal and rectosigmoid cancer incidence identified the beginning of the increase to be 1984. All races and both sexes demonstrated similar statistically significant increases in the incidence of rectal and rectosigmoid cancer. CONCLUSIONS: The incidence of rectal and rectosigmoid cancer appears to be increasing in patients aged <40 years. Patients presenting with rectal bleeding or other alarming signs or symptoms should be evaluated with this finding in mind.

Neoadjuvant therapy induces loss of MSH6 expression in colorectal carcinoma.

Immunohistochemical stains are routinely used to detect abnormal DNA mismatch repair (MMR) protein expression in colorectal carcinomas, particularly when Lynch syndrome is suspected. Complete loss of MMR protein expression is often associated with underlying microsatellite instability (MSI), and the combined results of mutL homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2), mutS homolog 2 (MSH2), or mutS homolog 6 (MSH6) immunostains may point to the defective MMR protein in tumors with MSI. We have noted that some neoadjuvantly treated colorectal carcinomas display loss of MMR protein immunoexpression, despite a lack of underlying MSI and preserved staining in pretreatment tumor samples. The purpose of this study was to determine the frequency of this finding. We identified 51 neoadjuvantly treated resected colorectal cancers. Posttreatment tumor samples were immunohistochemically stained with MLH1, PMS2, MSH2, and MSH6 antibodies. Loss of staining for any marker was followed by analysis for MSI and assessment of MMR protein expression in pretreatment tumor samples. All of the 51 posttreatment tumor samples showed preserved MLH1, PMS2, and MSH2, but 10 posttreatment tumor samples (20%) showed decreased MSH6 staining. Of these, 9 posttreatment tumor samples displayed loss of staining in less than 100% of tumor cells, but preserved MSH6 expression in pretreatment tumor samples. One case showed a complete absence of MSH6 staining in both pretreatment and posttreatment tumor samples. All 10 cases were microsatellite stable. We conclude that extensive loss of MSH6 immunoexpression is common among neoadjuvantly treated colorectal carcinomas, but generally does not reflect underlying MSI. Therefore, diminished MSH6 staining in treated tumors should prompt immunohistochemical evaluation of pretreatment biopsy samples before genetic testing for Lynch syndrome.

The role of dose escalation with intracavitary brachytherapy in the treatment of localized CNS malignancies: outcomes and toxicities of a prospective study.

PURPOSE: This single-institution prospective study was designed to investigate the feasibility and safety of dose escalation with GliaSite (Proxima Therapeutics Inc., Alpharetta, GA) brachytherapy for the treatment of patients with newly diagnosed and recurrent central nervous system (CNS) tumors after neurosurgical resection. We now report mature results of this trial, its outcomes, and a toxicity profile. METHODS AND MATERIALS: Ten adult consecutive patients with recurrent and newly diagnosed CNS malignancies underwent GliaSite brachytherapy after maximally safe neurosurgical resection between 2004 and 2007. GliaSite balloon was placed intraoperatively, and the size was selected so as to conform to the surgical cavity. Low-dose-rate radiation was delivered with an aqueous solution of organically bound (125)I (Iotrex: sodium 3-((125)I)-iodo-4-hydroxybenzenesulfonate; Proxima Therapeutics Inc.), introduced into the balloon portion of the device via a subcutaneous port. Two to 3 weeks later, the device was filled with Iotrex for a median dwell time of 94.3 hours (range, 68.0-120.5 hours), after which the balloon was explanted. A commercial 3-D planning system was used for a detailed analysis of dosimetry. Median dose of 52.0 Gy (range, 45.0-60.0 Gy) was prescribed 0.5-1.0 cm from the balloon surface. Radiation Therapy Oncology Group (RTOG) criteria were used to assess acute and long-term toxicities associated with this technique. Followup was assessed with MRI scans and was available on all enrolled patients. RESULTS: Median followup for surviving patients was 38 months (range, 18-57 months). Mean size of GliaSite balloon was 3.4 cm (range, 2.0-4.0 cm). Mean volume of filling was 19.0 cc (range, 4.0-35.0 cc). Median activity of Iotrex was 301.6 mCi (range, 95.0-515.4 mCi). Median survival was 14.0 months for the entire cohort after the treatment with the GliaSite device. Of our cohort, 6/10 (60%) patients sustained recurrence (20% local and 40% distant). Median time to recurrence after treatment with GliaSite was 8.0 months, and median time to death after recurrence was 7.5 months. There were no RTOG Grade 3 or 4 acute or late toxicities. Followup MRI imaging did not identify any evidence of radiation necrosis. CONCLUSIONS: Our data indicate that treatment with GliaSite balloon brachytherapy is feasible and safe, while rendering acceptable local control and minimal acute and long-term toxicities for newly diagnosed and recurrent CNS malignancies. These encouraging results compel us to embark on testing larger numbers of patients with this treatment modality.

Feasibility and safety of GliaSite brachytherapy in treatment of CNS tumors following neurosurgical resection.

PURPOSE: To investigate feasibility and safety of GliaSite brachytherapy for treatment of central nervous system (CNS) tumors following neurosurgical resection. We report mature results of long-term follow-up, outcomes and toxicity. MATERIALS AND METHODS: In the period from 2004 to 2007, 10 consecutive adult patients with recurrent, newly diagnosed, and metastatic brain malignancies underwent GliaSite brachytherapy following maximally safe neurosurgical resection. While 6/10 (60%) patients were treated for recurrence, having previously been treated with external beam radiotherapy (EBRT), 4/10 (40%) received radiotherapy (RT) for the first time. A median dose of 52.0 Gy (range, 45.0 - 60.0 Gy) was prescribed to 0.5 cm - 1.0 cm from the balloon surface. Radiation Therapy Oncology Group (RTOG) criteria were used to assess toxicities associated with this technique. Follow-up was assessed with MRI scans and was available on all enrolled patients. RESULTS: Median follow-up was 38 months (range, 18 - 57 months). Mean size of GliaSite balloon was 3.4 cm (range, 2.0 - 4.0 cm). Median survival was 14.0 months for the entire cohort after the treatment. The 17.6 and 16.0 months average survival for newly diagnosed and recurrent high grade gliomas (HGG), respectively, translated into a three-month improvement in survival in patients with newly diagnosed HGG compared to historical controls (P = 0.033). There were no RTOG grades 3 or 4 acute or late toxicities. Follow-up magnetic resonance imaging (MRI) imaging did not identify radiation necrosis. CONCLUSIONS: Our data indicate that treatment with GliaSite brachytherapy is feasible, safe and renders acceptable local control, acute and long-term toxicities. We are embarking on testing larger numbers of patients with this treatment modality.

Neoadjuvant radiation is associated with improved survival in patients with resectable pancreatic cancer: an analysis of data from the surveillance, epidemiology, and end results (SEER) registry.

PURPOSE: Cancer of the exocrine pancreas is the fifth leading cause of cancer death in the United States. Neoadjuvant chemoradiation has been investigated in several trials as a strategy for downstaging locally advanced disease to resectability. The aim of the present study is to examine the effect of neoadjuvant radiation therapy (RT) vs. other treatments on long-term survival for patients with resectable pancreatic cancer in a large population-based sample group. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results (SEER) registry database (1994-2003) was queried for cases of surgically resected pancreatic cancer. Retrospective analysis was performed. The endpoint of the study was overall survival. RESULTS: Using Kaplan-Meier analysis we found that the median overall survival of patients receiving neoadjuvant RT was 23 months vs. 12 months with no RT and 17 months with adjuvant RT. Using Cox regression and controlling for independent covariates (age, sex, stage, grade, and year of diagnosis), we found that neoadjuvant RT results in significantly higher rates of survival than other treatments (hazard ratio [HR], 0.55; 95% confidence interval, 0.38-0.79; p = 0.001). Specifically comparing adjuvant with neoadjuvant RT, we found a significantly lower HR for death in patients receiving neoadjuvant RT rather than adjuvant RT (HR, 0.63; 95% confidence interval, 0.45-0.90; p = 0.03). CONCLUSIONS: This analysis of SEER data showed a survival benefit for the use of neoadjuvant RT over surgery alone or surgery with adjuvant RT in treating pancreatic cancer. Therapeutic strategies that use neoadjuvant RT should be further explored for patients with resectable pancreatic cancer.