Phase II Evaluation of Stereotactic Ablative Radiotherapy (SABR) and Immunity in 11C-Choline-PET/CT-Identified Oligometastatic Castration-Resistant Prostate Cancer.

PURPOSE: Outcomes for resistant metastatic castration-resistant prostate cancer (CRPC) are poor. Stereotactic ablative radiotherapy (SABR) induces antitumor immunity in clinical and preclinical studies, but immunologic biomarkers are lacking. PATIENTS AND METHODS: Eighty-nine patients with oligometastatic CRPC were identified by 11C-Choline-PET (Choline-PET) from August 2016 to December 2019 and treated with SABR. Prespecified coprimary endpoints were 2-year overall survival (OS) and PSA progression. Secondary endpoints included 2-year SABR-treated local failure and 6-month adverse events. Correlative studies included peripheral blood T-cell subpopulations before and after SABR. RESULTS: 128 lesions in 89 patients were included in this analysis. Median OS was 29.3 months, and 1- and 2-year OS were 96% and 80%, respectively. PSA PFS was 40% at 1 year and 21% at 2 years. Local PFS was 84.4% and 75.3% at 1 and 2 years, respectively, and no grade ≥3 AEs were observed. Baseline high levels of tumor-reactive T cells (TTR; CD8+CD11ahigh) predicted superior local, PSA, and distant PFS. Baseline high levels of effector memory T cells (TEM; CCR7-CD45RA-) were associated with improved PSA PFS. An increase in TTR at day 14 from baseline was associated with superior OS. CONCLUSIONS: This is the first comprehensive effector T-cell immunophenotype analysis in a phase II trial before and after SABR in CRPC. Results are favorable and support the incorporation of immune-based markers in the design of future randomized trials in patients with oligometastatic CRPC treated with SABR.

Prospective Immunophenotyping of CD8+ T Cells and Associated Clinical Outcomes of Patients With Oligometastatic Prostate Cancer Treated With Metastasis-Directed SBRT.

PURPOSE: This study examined the effects of metastasis-directed stereotactic body radiation therapy (mdSBRT) on CD8+ T-cell subpopulations and correlated post-mdSBRT immunophenotypic responses with clinical outcomes in patients with oligometastatic prostate cancer (OPCa). METHODS AND MATERIALS: Peripheral blood mononuclear cells were prospectively isolated from 37 patients with OPCa (≤3 metastases) who were treated with mdSBRT. Immunophenotyping identified circulating CD8+ T-cell subpopulations, including tumor-reactive (TTR), effector memory, central memory (TCM), effector, and naïve T cells from samples collected before and after mdSBRT. Univariate Cox proportional hazards regression was used to assess whether changes in these T-cell subpopulations were potential risk factors for death and/or progression. The Kaplan-Meier method was used for survival. Cumulative incidence for progression and new distant metastasis weas estimated, considering death as a competing risk. RESULTS: Median follow-up was 39 months (interquartile range, 34-43). Overall survival at 3 years was 78.2%. Cumulative incidence for local progression and new distant metastasis at 3 years was 16.5% and 67.6%, respectively. Between baseline and day 14 after mdSBRT, an increase in the TCM cell subpopulation was associated with the risk of death (hazard ratio, 1.22 [95% confidence interval, 1.02-1.47]; P = .033), and an increase in the TTR cell subpopulation was protective against the risk of local progression (hazard ratio, 0.80 [95% confidence interval, 0.65-0.98]; P = .032). CONCLUSIONS: An increase in the TTR cell subpopulation was protective against the risk of disease progression, and an increase in the TCM cell subpopulation was associated with the risk of death in patients with OPCa treated with mdSBRT. Disease control may be further improved by better understanding the CD8+ T-cell subpopulations and by enhancing their antitumor effect.

N08C9 (Alliance): A Phase 3 Randomized Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy.

PURPOSE: To provide confirmatory evidence on the use of sulfasalazine to reduce enteritis during pelvic radiation therapy (RT), following 2 prior single-institution trials suggestive that benefit existed. METHODS AND MATERIALS: A multi-institution, randomized, double-blind, placebo-controlled phase 3 trial was designed to assess the efficacy of sulfasalazine versus placebo in the treatment of RT-related enteritis during RT including the posterior pelvis (45.0-53.5 Gy) and conducted through a multicenter national cooperative research alliance. Patients received 1000 mg of sulfasalazine or placebo orally twice daily during and for 4 weeks after RT. The primary endpoint was maximum severity of diarrhea (Common Terminology Criteria for Adverse Events version 4.0). Toxicity and bowel function were assessed by providers through a self-administered bowel function questionnaire taken weekly during RT and for 6 weeks afterward. RESULTS: Eighty-seven patients were enrolled in the trial between April 29, 2011, and May 13, 2013, with evenly distributed baseline factors. At the time of a planned interim toxicity analysis, more patients with grade ≥3 diarrhea received sulfasalazine than received placebo (29% vs 11%, P=.04). A futility analysis showed that trial continuation would be unlikely to yield a positive result, and a research board recommended halting study treatment. Final analysis of the primary endpoint showed no significant difference in maximum diarrhea severity between the sulfasalazine and placebo arms (P=.41). CONCLUSIONS: Sulfasalazine does not reduce enteritis during pelvic RT and may be associated with a higher risk of adverse events than placebo. This trial illustrates the importance of confirmatory phase 3 trials in the evaluation of symptom-control agents.

Angiosarcoma of the seminal vesicle: a case report of long-term survival following multimodality therapy.

Angiosarcoma of the seminal vesicle is an extremely rare malignancy, with few published case reports in the literature. We present a case of primary angiosarcoma of the seminal vesicle in a 45-year-old male who was treated with multimodality therapy, consisting of neoadjuvant chemotherapy and chemoradiation followed by surgical resection and intraoperative radiation therapy. He has been free of cancer recurrence for more than six years after completion of therapy. To our knowledge, this represents the longest reported survival of a patient with this rare tumor, and one of the few cases reported using a multimodality therapy approach.

An unusual case of isolated, serial metastases of gallbladder carcinoma involving the chest wall, axilla, breast and lung parenchyma.

In the English literature, only 9 cases of adenocarcinoma of the gallbladder with cutaneous metastasis have been reported so far. One case of multiple cutaneous metastases along with deposits in the breast tissue has been reported. We present a case of incidental metastatic gallbladder carcinoma with no intra-abdominal disease presenting as a series of four isolated cutaneous right chest wall, axillary nodal, breast, and pulmonary metastases following resection and adjuvant chemoradiation for her primary tumor. In spite of the metastatic disease coupled with the aggressive nature of the cancer, this patient reported that her energy level had returned to baseline with a good appetite and a stable weight indicating a good performance status and now is alive at 25 months since diagnosis. Her serially-presented, oligometastatic diseases were well-controlled by concurrent chemoradiotherapy and stereotactic radiation therapy. We report this case study because of its rarity and for the purpose of complementing current literature with an additional example of cutaneous metastasis from adenocarcinoma of the gallbladder.

Recurrent invasive lobular carcinoma presenting as a ruptured breast implant.

BACKGROUND: For years, the treatment for invasive lobular carcinoma (ILC) has been mastectomy secondary to the lack of studies investigating the efficacy of breast conservation therapy on patients afflicted with ILC and due to the lack of long-term follow up investigating locoregional recurrence in this patient population. In this article we report the clinical course of a patient diagnosed with ILC. CASE REPORT: We describe the case of a 50-year-old woman with stage IIB (T2N1M0) ER/PR positive right breast ILC who underwent a right modified radical mastectomy, postoperative chemotherapy, a prophylactic left simple mastectomy with bilateral breast reconstruction and tamoxifen. Approximately 12 years later, she presented with a deflated breast implant and recurrent breast cancer with metastatic spread. She received palliative radiotherapy then palliative chemotherapy. Unfortunately, she succumbed to the cancer less than a year after being diagnosed with metastatic disease. CONCLUSIONS: This may be the first case report of a ruptured breast implant presenting at the same time as the diagnosis of recurrent breast cancer.

Adjuvant chemoradiotherapy for resected pancreas cancer.

The purpose of this article is to review pertinent literature assessing the evidence regarding adjuvant chemoradiotherapy for adenocarcinoma of the pancreas following curative resection. This review looks at randomized controlled studies with the emphasis on adjuvant chemoradiotherapy. In assessing the evidence from the studies reviewed in this article, the trials have been grouped according to the positive or negative results for or against adjuvant treatment. In addition, data from two large, single-institution studies affirming the role for adjuvant chemoradiotherapy has been included. Understanding the evidence from all of the randomized studies is important in shaping current practice recommendations for adjuvant therapy of surgically resected pancreas cancer. Adjuvant chemoradiotherapy following surgery is the current approach at many cancer treatment centers in the United States. In Europe, chemotherapy alone is the preferred adjuvant therapy. However, the type of adjuvant treatment recommended remains controversial due to conflicting study results. The debate will likely continue. Current practice should be based on the weight of evidence available at this time, which is in favor of adjuvant chemotherapy with chemoradiotherapy.

Review of adjuvant radiochemotherapy for resected pancreatic cancer and results from Mayo Clinic for the 5th JUCTS symposium.

PURPOSE: To present an overview of Phase III trials in adjuvant therapy for pancreatic cancer and review outcomes at the Mayo Clinic after adjuvant radiochemotherapy (RT/CT) for resected pancreatic cancer. METHODS AND MATERIALS: A literature review and a retrospective review of 472 patients who underwent an R0 resection for T1-3N0-1M0 invasive carcinoma of the pancreas from 1975 to 2005 at the Mayo Clinic, Rochester, MN. Patients with metastatic or unresectable disease at the time of surgery, positive surgical margins, or indolent tumors and those treated with intraoperative radiotherapy were excluded from the analysis. Median radiotherapy dose was 50.4 Gy in 28 fractions, with 98% of patients receiving concurrent 5-fluorouracil- based chemotherapy. RESULTS: Median follow-up was 2.7 years. Median overall survival (OS) was 1.8 years. Median OS after adjuvant RT/CT was 2.1 vs. 1.6 years for surgery alone (p = 0.001). The 2-y OS was 50% vs. 39%, and 5-y was 28% vs. 17% for patients receiving RT/CT vs. surgery alone. Univariate and multivariate analysis revealed that adverse prognostic factors were positive lymph nodes (risk ratio [RR] 1.3, p < 0.001) and high histologic grade (RR 1.2, p < 0.001). T3 tumor status was found significant on univariate analysis only (RR 1.1, p = 0.07). CONCLUSIONS: Results from recent clinical trials support the use of adjuvant chemotherapy in resected pancreatic cancer. The role of radiochemotherapy in adjuvant treatment of pancreatic cancer remains a topic of debate. Results from the Mayo Clinic suggest improved outcomes after the administration of adjuvant radiochemotherapy after a complete resection of invasive pancreatic malignancies.

Evidence-based guidelines for adjuvant therapy for resected adenocarcinoma of the pancreas.

Pancreatic cancer, the fourth most common cause of cancer deaths, has a five-year survival rate of 5% or less. Surgical removal of the tumor may improve survival, but survival remains poor even in optimally resected patients. The best adjuvant therapy for patients with resected pancreatic cancer is not clear. Surgical resection followed by chemoradiation and maintenance chemotherapy has been considered the most beneficial treatment for improving survival, but more recent studies have suggested that chemotherapy alone is more effective. The purpose of this article is to review randomized controlled studies of adjuvant chemoradiation or chemotherapy alone in the treatment of resected pancreatic cancer and to determine the optimal adjuvant therapy after curative resection with negative or microscopically positive margins. The outcomes of interest were overall survival and disease-free survival. The results indicate that chemoradiation is an acceptable option for adjuvant treatment. Three of the four randomized controlled trials suggest that adjuvant chemoradiation for resected pancreatic cancer improves overall survival. Adding gemcitabine to the chemoradiation regimen also confers increased disease-free survival. Providers counseling patients regarding treatment options for resected pancreatic cancer should continue to recommend adjuvant therapy--a combination of chemotherapy including gemcitabine and radiotherapy--for appropriately selected patients.

Adjuvant radiotherapy and chemotherapy for pancreatic carcinoma: the Mayo Clinic experience (1975-2005).

PURPOSE: To determine prognostic factors and impact of adjuvant chemotherapy (CT) and radiotherapy (RT) on overall survival (OS) after resection of pancreatic adenocarcinoma. PATIENTS AND METHODS: We performed a retrospective review 472 consecutive patients who underwent complete resection with negative margins (R0) for invasive carcinoma (T1-3N0-1M0) of the pancreas between 1975 and 2005 at the Mayo Clinic in Rochester, MN. Exclusion criteria included metastatic or unresectable disease at surgery, positive surgical margins, and indolent tumor types (islet cell tumors and mucinous cystadenocarcinoma). Median RT dose was 50.4 Gy in 28 fractions; 98% of RT patients also received concurrent fluorouracil-based CT. RESULTS: Six patients died within 30 days of surgery. For the 466 surviving patients, median follow-up was 32.4 months; median OS was 21.6 months. Median OS after adjuvant CT-RT was 25.2 versus 19.2 months after no adjuvant therapy (P = .001). Two-year OS was 50% versus 39%, and 5-year OS was 28% versus 17%. Adverse prognostic factors identified by univariate and multivariate analysis included positive lymph nodes (risk ratio [RR] = 1.3; P < .001), high histologic grade (RR = 1.2; P < .001), and no adjuvant therapy (RR = 1.3; P < .001). Tumor extension beyond the pancreas was an adverse prognostic factor by univariate analysis alone (P = .03). Patients receiving adjuvant therapy had more adverse prognostic factors than those not receiving adjuvant therapy (P = .001). CONCLUSION: This study represents one of the largest, single-institution, retrospective reviews of adjuvant therapy in patients after R0 resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CT-RT.