Iott, Matthew J.

Abstract 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.

562 Background: An interim futility analysis at ASTRO 2013 led to early closure of N08C9 (Alliance), a randomized controlled trial (RCT) comparing sulfasalazine (SSZ) versus placebo (PBO) in the prevention of radiation enteritis during pelvic RT. This is the full analysis of the primary endpoint (PE) and secondary endpoints (SEs) of the trial. Methods: A multi-institutional RCT conducted by the Alliance for Clinical Trials in Oncology assessed the effect of 1000 mg SSZ b.i.d. versus PBO b.i.d. in the treatment of pelvic RT related enteritis. Study participants (SPs) received the study agents during RT and for 4 weeks afterwards. The PEwas the maximal severity of diarrhea toxicity (CTCAE version 4.0) during and up to 6 weeks after RT. SEs, including the maximum severity of diarrhea (MSD) and the duration of MSD, rectal bleeding, abdominal cramping, tenesmus, and constipation, were graded weekly during RT by a health care provider. Bowel function was assessed using a self-administered bowel function questionnaire weekly during RT, afterwards at 6 weeks, and at 12 and 24 months. A two-sided 0.05-level Wilcoxon rank-sum test was used to test the equality of the distributions of MSD grades. The planned study size was 128 SPs. Results: 87 SPs were enrolled in the study between 4/29/2011 and 5/13/2013, with evenly distributed baseline factors. Toxicity data were available in 84 SPs during RT and in 54 SPs in the 6 weeks following RT. There was no significant difference in the distribution of MSD grades between the SSZ and PBO arms (p=0.41 regardless of attribution; p=0.09 at least possibly attributed to the study agent). No significant differences were observed in SEs during RT and after RT, except the abdominal pain occurring after completion of RT was higher in SPs receiving SSZ (p=0.02). More SPs required antidiarrheal agents on the SSZ arm (49% vs. 29%, p=0.06). Conclusions: Despite prior single institution RCT’s suggesting a benefit for SSZ (Kilic 2001; Pal 2013) in this clinical context, the results of this large, multi-institutional trial demonstrate that SSZ does not reduce the risk of enteritis and may worsen acute GI toxicity during pelvic RT. Clinical trial information: NCT01198145.

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.

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.

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.