Libni Eapen

Final report of multicenter Canadian Phase III randomized trial of 3 versus 8 months of neoadjuvant androgen deprivation therapy before conventional-dose radiotherapy for clinically localized prostate cancer.

PURPOSE To evaluate the effect of 3 vs. 8 months of neoadjuvant hormonal therapy before conventional-dose radiotherapy (RT) on disease-free survival for localized prostate cancer. METHODS AND MATERIALS Between February 1995 and June 2001, 378 men were randomized to either 3 or 8 months of flutamide and goserelin before 66 Gy RT at four participating centers. The median baseline prostate-specific antigen level was 9.7 ng/mL (range, 1.3-189). Of the 378 men, 26% had low-, 43% intermediate-, and 31% high-risk disease. The two arms were balanced in terms of age, Gleason score, clinical T category, risk group, and presenting prostate-specific antigen level. The median follow-up for living patients was 6.6 years (range, 1.6-10.1). Of the 378 patients, 361 were evaluable, and 290 were still living. RESULTS The 5-year actuarial freedom from failure rate for the 3- vs. 8-month arms was 72% vs. 75%, respectively (p = 0.18). No difference was found in the failure types between the two arms. The median prostate-specific antigen level at the last follow-up visit for patients without treatment failure was 0.6 ng/mL in the 3-month arm vs. 0.50 ng/mL in the 8-month arm. The disease-free survival rate at 5 years was improved for the high-risk patients in the 8-month arm (71% vs. 42%, p = 0.01). CONCLUSION A longer period of NHT before standard-dose RT did not alter the patterns of failure when combined with 66-Gy RT. High-risk patients in the 8-month arm had significant improvement in the 5-year disease-free survival rate.

Early-stage squamous cell carcinoma of the oropharynx: Radiotherapy vs. Trans-Oral Robotic Surgery (ORATOR) – study protocol for a randomized phase II trial

BackgroundThe incidence of oropharyngeal squamous cell carcinoma (OPSCC) has markedly increased over the last three decades due to newly found associations with human papillomavirus (HPV) infection. Primary radiotherapy (RT) is the treatment of choice for OPSCC at most centers, and over the last decade, the addition of concurrent chemotherapy has led to a significant improvement in survival, but at the cost of increased acute and late toxicity. Transoral robotic surgery (TORS) has emerged as a promising alternative treatment, with preliminary case series demonstrating encouraging oncologic, functional, and quality of life (QOL) outcomes. However, comparisons of TORS and RT in a non-randomized fashion are susceptible to bias. The goal of this randomized phase II study is to compare QOL, functional outcomes, toxicity profiles, and survival following primary RT (± chemotherapy) vs. TORS (± adjuvant [chemo] RT) in patients with OPSCC.Methods/DesignThe target patient population comprises OPSCC patients who would be unlikely to require chemotherapy post-resection: Tumor stage T1-T2 with likely negative margins at surgery; Nodal stage N0-2, ≤3 cm in size, with no evidence of extranodal extension on imaging. Participants will be randomized in a 1:1 ratio between Arm 1 (RT ± chemotherapy) and Arm 2 (TORS ± adjuvant [chemo] RT). In Arm 1, patients with N0 disease will receive RT alone, whereas N1-2 patients will receive concurrent chemoradiation. In Arm 2, patients will undergo TORS along with selective neck dissections, which may be staged. Pathologic high-risk features will be used to determine the requirement for adjuvant radiotherapy +/- chemotherapy. The primary endpoint is QOL score using the M.D. Anderson Dysphagia Inventory (MDADI), with secondary endpoints including survival, toxicity, other QOL outcomes, and swallowing function. A sample of 68 patients is required.DiscussionThis study, if successful, will provide a much-needed randomized comparison of the conventional strategy of primary RT vs. the novel strategy of primary TORS. The trial is designed to provide a definitive QOL comparison between the two arms, and to inform the design of an eventual phase III trial for survival outcomes.Trial registrationNCT01590355

Adjuvant radiotherapy following radical prostatectomy for pathologic T3 or margin-positive prostate cancer: A systematic review and meta-analysis

BACKGROUND AND PURPOSE Results following radical prostatectomy (RP) are suboptimal in patients found to have cancer extending beyond the prostatic capsule (pT3) or present at the resection margins (R1). The optimal postoperative management of such patients is undefined. Therapeutic alternatives include adjuvant radiotherapy (RT) or active surveillance. METHODS Randomized controlled trials (RCTs) were eligible for inclusion in this systematic review if they compared adjuvant RT in the immediate period after RP to active surveillance - with therapies held in reserve for salvage - in prostate cancer patients with pT3 or R1 disease or both. The primary outcome of interest was overall survival. RESULTS Three RCTs representing 1,743 patients satisfied the eligibility criteria. Two trials reported data on overall survival; a meta-analysis of the data showed no significant improvement associated with adjuvant RT (hazard ratio=0.91, 95% CI 0.67-1.22, p=0.52). All trials reported data on biochemical progression-free survival (bPFS). On meta-analysis, adjuvant RT significantly improved bPFS (hazard ratio=0.47, 95% CI 0.40-0.56, p<0.00001). One trial provided comparative graded toxicity data; there were no significant differences between arms in severe (grade 3) gastrointestinal or genitourinary toxicity at five years. CONCLUSIONS To date, adjuvant RT has not been shown to improve overall survival compared with active surveillance. Longer follow-up from completed RCTs is required to accurately assess this outcome. Adjuvant RT does, however, significantly improve bPFS and is not associated with excess severe late toxicity.

Twenty-four-month postradiation prostate biopsies are strongly predictive of 7-year disease-free survival: results from a Canadian randomized trial.

The objective of this study was to evaluate the predictive value of prostate biopsies that were obtained 24 months after the completion of radiotherapy (RT) with respect to disease‐free survival (DFS) in a randomized trial that compared 3 months versus 8 months of neoadjuvant hormone therapy before conventional dose external RT.

Intraarterial cisplatin and concurrent radiation for locally advanced bladder cancer.

Between 1983 and 1987 25 patients with invasive bladder cancer (16 stage tumor 3 (T3) and nine stage T4) were treated with intraarterial cisplatin and concurrent radical radiation (20/25) or intraarterial cisplatin, concurrent preoperative radiation, and cystectomy (5/25). One patient died from treatment-related toxicity. Other toxicities have been what one would expect from the individual treatment modalities except for a sensory sacral root neuropathy in 11 of 24 (46%) patients. Twenty-three of 24 (96%) patients achieved a complete response (CR) and the projected actuarial 2-year survival is 90%. Only one of the 23 complete responders has had an invasive local recurrence. The excellent complete local response and survival rates achieved warrant further study of the combination of intraarterial cisplatin and radiation as a bladder-preserving strategy.

Smoking is associated with worse outcomes in patients with prostate cancer treated by radical radiotherapy

To investigate the effect of smoking on the outcome in a cohort of men treated for localized prostate cancer at one institution with a uniform protocol of radical external beam radiotherapy (EBRT).

Management and outcome differences in supraglottic cancer between Ontario, Canada, and the Surveillance, Epidemiology, and End Results areas of the United States.

PURPOSE We compared the management and outcome of supraglottic cancer in Ontario, Canada, with that in the Surveillance, Epidemiology, and End Results (SEER) Program areas in the United States. METHODS Electronic, clinical, and hospital data were linked to cancer registry data and supplemented by chart review where necessary. Stage-stratified analyses compared initial treatment and survival in the SEER areas (n = 1,643) with a random sample from Ontario (n = 265). We also compared laryngectomy rates at 3 years in those patients 65 years and older at diagnosis. RESULTS Radical surgery was more commonly used in SEER, with absolute differences increasing with increasing stage: I/II, 17%; III, 36%; and IV, 45%. The 5-year survival rates were 74% in Ontario and 56% in SEER for stage I/II disease (P =.01), 55.7% in Ontario and 46.8% in SEER for stage III disease (P =.40), and 28.5% in Ontario and 29.1% in SEER for stage IV disease (P =.28). Cancer-specific survival results mirrored the overall survival results with the exception of stage IV disease, for which 34.6% of Ontario patients survived their cancer compared with 38.1% in SEER (P =.10). This stage IV difference was more pronounced when we further controlled for possible cause of death errors by restricting the comparison to patients with a single primary cancer (P =.01). Three-year actuarial laryngectomy rates differed. In stage I/II, these rates were 3% in Ontario compared with 35% in SEER (P < 10(-3)). In stage III disease, the rates were 30% and 54%, respectively (P =.03), and in stage IV disease they were 33% and 64% (P =.002). CONCLUSION There are large differences in the management of supraglottic cancer between the SEER areas of the United States and Ontario. Long-term larynx retention was higher in Ontario, where radiotherapy is widely regarded as the treatment of choice and surgery is reserved for salvage. In stages I to III, survival was similar in the two regions despite the differences in treatment policy. In stage IV, there may be a small survival advantage in the U.S. SEER areas related to the higher use of primary surgery.

Cisplatin and radiation in the treatment of tumors of the central nervous system: pharmacological considerations and results of early studies

PURPOSE To review the human central nervous system pharmacology of cisplatin, factors that affect cisplatin uptake in tumors, and use alone and with radiation for the treatment of primary brain tumors. METHODS AND MATERIALS The authors review their own prior published and unpublished experience and data published by other groups on the above issues. RESULTS Cisplatin is one of the most active chemotherapy drugs available for the treatment of solid tumors. It is synergistic with several other agents, including radiation. While it attains only low concentrations in the normal central nervous system, concentrations and plasma-tissue transfer constants for human intracerebral tumors are comparable to those in extracerebral tumors. Tumor type appears to be a more important determinant of platinum concentration than is tumor location, and gliomas do achieve lower concentrations than do other intracerebral or extracerebral tumors. Several other factors have also been identified that correlate with concentrations of cisplatin achieved in human tumors. While cisplatin alone and in combination with other drugs does have some degree of efficacy against primary brain tumors, combining it with cranial irradiation has generally not resulted in any substantial improvement in outcome to date, although some individual studies have been somewhat encouraging. New approaches are currently under investigation. CONCLUSION Human pharmacology studies provide a rationale for use of cisplatin in the treatment of human brain tumors, and human and in vitro studies suggest some manipulations that might potentially further augment tumor platinum concentrations. While clinical studies suggest that cisplatin combinations may be of some value vs. human primary brain tumors and brain metastases, and while in vitro studies suggest that cisplatin potentiates radiation efficacy, no combination of cisplatin plus radiation yet tested has appeared to be superior to radiation alone.

The role of computed tomography in the T classification of laryngeal carcinoma

The objectives of this study were 1) to describe patterns of use of computed tomography (CT) in laryngeal carcinoma, and 2) to characterize the contribution of CT to the T classification of laryngeal carcinoma.

Pilot Study on Quality of Life and Sexual Function in Men-Who-Have-Sex-with-Men Treated for Prostate Cancer

INTRODUCTION There is limited data on post-treatment quality of life (QoL) for men-who-have-sex-with-men (MSM) with prostate cancer (PCa). QoL in MSM may not be reflected by assessment tools designed for the heterosexual population. AIMS Our goals were to evaluate post-treatment QoL in PCa patients who are MSM, and to investigate the utility of current QoL assessment tool. METHODS PCa patients treated with surgery and/or radiation were recruited from the local MSM community. Each participant completed the Expanded Prostate Cancer Index Composite (EPIC) questionnaire, Male Sexual Health Questionnaire (MSHQ), and a questionnaire focused on insertive and receptive roles of anal intercourse. MAIN OUTCOME MEASURES Response scores were calculated based on questionnaire design and compared by treatment modality. RESULTS Seven participants treated with surgery (mean age 58) and eight participants treated with radiation (mean age 67) were recruited. No participant in the surgical group received androgen deprivation therapy (ADT) while two in radiation group were treated with ADT. The sample size of this study did not permit formal statistical analysis, although potential differences in Urinary and Bowel Domains from EPIC and Ejaculation Scale from MSHQ were observed. More participants from the radiation group seemed to be able to maintain both insertive and receptive anal intercourse roles after treatment compared to participants who received surgery. CONCLUSIONS While the two validated assessment tools suggested similar QoL scores including sexual function for both surgical and radiation groups, post-treatment sexual function related to anal intercourse may be better in the radiation group, as compared to the surgical group. Larger studies in PCa patients from MSM community are warranted to verify these data.