Clinical outcomes of melanoma brain metastases treated with stereotactic radiosurgery and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitor, or conventional chemotherapy.

BACKGROUND: The effect of immunologic and targeted agents on intracranial response rates in patients with melanoma brain metastases (MBMs) is not yet clearly understood. This report analyzes outcomes of intact MBMs treated with single-session stereotactic radiosurgery (SRS) and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors(i), BRAFi, or conventional chemotherapy. PATIENTS AND METHODS: Patients were included if MBMs were treated with single-session SRS within 3 months of receiving systemic therapy. The primary end point of this study was distant MBM control. Secondary end points were local MBM control defined as a >20% volume increase on follow-up MRI, systemic progression-free survival, overall survival (OS) from both SRS and cranial metastases diagnosis, and neurotoxicity. Images were reviewed alongside two neuro-radiologists at our institution. RESULTS: Ninety-six patients were treated to 314 MBMs over 119 SRS treatment sessions between January 2007 and August 2015. No significant differences were noted in age (P = 0.27), gender (P = 0.85), treated gross tumor volume (P = 0.26), or the diagnosis-specific graded prognostic assessment (P = 0.51) between the treatment cohorts. Twelve-month Kaplan-Meier (KM) distant MBM control rates were 38%, 21%, 20%, 8%, and 5% (P = 0.008) for SRS with anti-PD-1 therapies, anti-CTLA-4 therapy, BRAF/MEKi, BRAFi, and conventional chemotherapy, respectively. No significant differences were noted in the KM local MBM control rates among treatment groups (P = 0.25). Treatment with anti-PD-1 therapy, anti-CTLA-4 therapy, or BRAF/MEKi significantly improved OS on both univariate and multivariate analyses when compared with conventional chemotherapy. CONCLUSION: In our institutional analysis of patients treated with SRS and various systemic immunologic and targeted melanoma agents, significant differences in distant MBM control and OS are noted. Prospective evaluation of the potential synergistic effect between these agents and SRS is warranted.

Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy.

BACKGROUND: The anti-programmed death-1 (anti-PD-1) therapy nivolumab has significant clinical activity in patients with metastatic melanoma. However, little is known about the safety and outcomes in patients receiving anti-PD-1 therapy and stereotactic radiation for the treatment of brain metastases (BMs). PATIENTS AND METHODS: Data were analyzed retrospectively from two prospective nivolumab protocols enrolling 160 patients with advanced resected and unresectable melanoma at a single institution. Patients were included if BMs were diagnosed and treated with stereotactic radiation within 6 months of receiving nivolumab. The primary end point of this study was neurotoxicity; secondary end points included BM control and survival. RESULTS: Twenty-six patients with a total of 73 BMs treated over 30 sessions were identified. Radiation was administered before, during and after nivolumab in 33 lesions (45%), 5 lesions (7%), and 35 lesions (48%), respectively. All BMs were treated with stereotactic radiosurgery (SRS) in a single session except 12 BMs treated with fractionated stereotactic radiation therapy, nine of which were in the postoperative setting. One patient experienced grade 2 headaches following SRS with symptomatic relief with steroid treatment. No other treatment-related neurologic toxicities or scalp reactions were reported. Eight (11%) local BM failures with a ≥20% increase in volume were noted. Of these lesions, hemorrhage was noted in 4, and edema was noted in 7. Kaplan-Meier estimates for local BM control following radiation at 6 and 12 months were 91% and 85%, respectively. Median overall survival (OS) from the date of stereotactic radiation and nivolumab initiation was 11.8 and 12.0 months, respectively, in patients receiving nivolumab for unresected disease (median OS was not reached in patients treated in the resected setting). CONCLUSIONS: In our series, stereotactic radiation to melanoma BMs is well tolerated in patients who received nivolumab. BM control and OS appear prolonged compared with standard current treatment. Prospective evaluation is warranted.

Prolonged survival after episiotomy recurrence of cervical cancer complicating pregnancy.

BACKGROUND: We report a case of recurrent cervical cancer in an episiotomy scar and the late treatment-related sequelae. CASE: Cervical cancer was diagnosed following a vaginal delivery, and was treated with surgery and radiotherapy. The patient developed a recurrence in her episiotomy scar, and was treated with chemoradiation. She remains without evidence of disease ten years later. CONCLUSION: Successful treatment of recurrent cervical cancer with chemoradiation is possible, but may be associated with significant normal tissue toxicity.

Grade migration in prostate cancer: an analysis using the Surveillance, Epidemiology, and End Results registry.

To utilize the Surveillance, Epidemiology, and End Results (SEER) registry to examine trends in grade assignment. Data from 411 325 patients from 1984 to 2003 were analyzed for grade migration and for cause-specific survival (CSS) as a function of grade. There has been a significant grade migration during the study period (P<0.001), principally from well-differentiated (WD) to moderately differentiated (MD) disease. Five-year CSS of MD and WD patients have converged, suggesting a decreasing role of grade as a prognostic factor. A grade migration from WD to MD assignment has occurred, suggesting that prognostic categorizations based on grade across eras may be difficult to interpret.

'Insignificant' prostate cancer on biopsy: pathologic results from subsequent radical prostatectomy.

'Insignificant' prostate cancer is defined as disease of virulence insufficient to threaten survival. In this review, which describes nine articles and two abstracts discussing almost 800 cases, we discuss the correlation of such 'insignificant' biopsy findings in the context of subsequent radical prostatectomy data. From our review, minimal disease on biopsy does not reliably predict minimal disease in the subsequent prostatectomy specimen, in terms of the size and grade of tumor, extracapsular extension or positive margins. Thus, reasoned accounting should be made of other data before undertaking a course of radiation therapy as monotherapy, particularly prostate-specific antigen kinetics and potential molecular markers.

Lack of survival benefit of post-operative radiation therapy in prostate cancer patients with positive lymph nodes.

Randomized data from SWOG 8794 and EORTC 22911 confirm the benefit of post-operative radiation therapy (RT) for selected patients with pT3 prostate cancer (CaP) after radical prostatectomy (RP). However, data regarding the potential benefit of RT for patients post-RP with positive lymph node (+LN) involvement are limited. We analyzed the Surveillance Epidemiology End Results (SEER) registry for population-based data on efficacy of post-operative RT for +LN patients after RP. As LN data have only been captured by SEER since 1988, we analyzed data for 1988-1992, with specific attention to 10-year relative survival (defined as observed survival divided by the survival of a gender-, age- and race-matched population cohort without disease). Specifically analyzed were data for 1921 patients with nonmetastatic prostate cancer who underwent surgery alone, or surgery followed by RT, and who had +LNs documented. SEER does not code the interval between surgery and RT, so the ratio of patients receiving salvage versus adjuvant therapy is unknown. Using follow-up data through 2002, post-diagnosis survival was examined by number of +LNs. There was no significant relative survival benefit for +LN patients receiving post-operative RT (chi(2)P=0.270). These data do not support routine use of post-operative RT for patients with +LNs in the surgical specimen.

The 100-day PSA: usefulness as surrogate end point for biochemical disease-free survival after definitive radiotherapy of prostate cancer.

Overall and biochemical disease-free (bNED) survival data after definitive radiotherapy (RT) for prostate cancer (CaP) requires decades of patient follow-up. Surrogates involving dynamics of prostate-specific antigen (PSA) decline, PSA nadir and time thereto have been unrewarding. This study investigated the metric of the PSA value 100 days after RT (PSA(100)), analyzed with respect to 8-y bNED survival. A total of 214 patients with T1-3 CaP were treated with definitive RT (defined as dose >66 Gy) in our institution between 1/1/1988 and 12/31/2000. All were subject to continuous follow-up with routine PSA levels. Biochemical failure (77 patients) was defined by the ASTRO criteria (n=67) or by the date of first hormonal therapy for a rising PSA, which did not meet the ASTRO criteria (n=10). No patients were included if they received postoperative radiation, or if hormones were administered prior to bNED recurrence, if any. Patients were stratified by PSA(100) values 4.0 ng/ml, and 4.0 ng/ml had 20% 8-y bNED survival (P<0.001). Use of a PSA(100) cutoff of 2.5 ng/ml yielded no significant difference in 8-y bNED survival (P=0.229). Cox proportional analysis revealed that initial PSA (P=0.006), stage (P=0.001) and PSA(100)

Treatment modalities of bladder/prostate rhabdomyosarcoma: a review.

Treatment outcomes of bladder/prostate rhabdomyosarcoma (RMS) in multi- and single-institutional trials are reviewed. Remarkable strides have occurred in the treatment of this disease. Decreasing duration of chemotherapy, less cumulative doses of radiation therapy, and improving survival have been documented. A focus on bladder preservation has not adversely affected survival in most studies. Even if organ preservation is not possible, improvements in urinary diversion surgical technique still offer improved quality of life. The IRS III was a pivotal study in improving survival and quality of life. We recommend protocol enrollment whenever available. We also emphasize the use of magnetic resonance imaging and second look surgery.

Initiation of salvage therapy for prostate cancer.

Physicians and patients have variable and individual levels of comfort regarding when to begin salvage therapy for rising prostate specific antigen (PSA) after definitive treatment of prostate cancer. The decision to start salvage therapy is a multifactorial process for which few rigorous data or guidelines exist. A questionnaire survey of urologists of the Department of Defense (DoD) Center for Prostate Disease Research (CPDR) was undertaken to obtain current perspectives on when to begin salvage therapy for biochemical failure after definitive therapy. Variables of age, grade, T-stage, nodal status, performance status, latency since prior therapy, PSA velocity, and ploidy were prioritized in four clinical situations; subsequent questions assessed consensus PSA cut-offs for beginning adjuvant therapy in 84 clinical scenarios. Consensus on PSA cut-off points was limited to postoperative radiotherapy (RT), where values of 1.0-1.5 were the mean cut-off points. CPDR urologists consider salvage prostatectomy post-RT only for patients <70-y-old with node negative, grade 2-7 disease and excellent performance status. Ploidy was not generally considered useful in any scenario. Many variables in addition to PSA level are involved in the decision of when to commence adjuvant therapy for initial biochemical failure. These are strikingly interdependent, and few clear absolutes are evident from this questionnaire. This is a point of necessary further research and continued discussion among physicians caring for these patients.

Management of recurrent colorectal carcinoma.

BACKGROUND/OBJECTIVE: The records of patients treated for adenocarcinoma of the colon and rectum between 1 January 1988 and 31 December 1995 at Naval Medical Center San Diego were reviewed. Analysis was made of patients who developed recurrences after potentially definitive primary therapy. METHODS: A retrospective review of 410 patients diagnosed with colorectal cancer at our institution was conducted. The focus of this review was to identify patients with recurrent disease after curative initial procedures, and to determine how recurrences were detected and treated. Survival data for 48 patients undergoing various curative and palliative procedures, or no therapy, were generated. RESULTS: The decision to re-operate with curative intent was made after a multidisciplinary review of restaging studies. Laparoscopy was not used in this determination. Curative resection of recurrence confers increased survival over non-curative surgery and no surgery (P < 0.001). This is misleading because of patient selection; several patients undergo potentially curative surgery but are determined intraoperatively to best be palliated, or to have further surgery aborted. Analysis of results in patients undergoing potentially curative surgery vs. those undergoing planned palliation vs. those not operated reveals that these also provide significantly different outcomes (P < 0.003). CONCLUSIONS: Proper delineation of resectable lesions in patients with recurrent colorectal cancer contributes to better outcomes for them. That determination is difficult, and efforts are underway in our institution and elsewhere to better delineate which patients are optimal preoperatively. We consider multidisciplinary Tumor Board evaluation to be central to this process.