Salvage Cryoablation for Radiorecurrent Prostate Cancer: Initial Experience at a Regional Health Care System.

CONTEXT: Local recurrence after radiotherapy for prostate cancer remains challenging to treat effectively. Although oncologic control is highest with salvage prostatectomy, the procedure is associated with substantial morbidity. OBJECTIVE: To identify factors associated with successful salvage cryoablation for radiorecurrent prostate cancer. DESIGN: We retrospectively reviewed the medical records of patients who underwent salvage cryoablation at our institution between 2005 and 2015. All patients had biopsy-proven local recurrence after radiotherapy. Patients with seminal vesicle invasion or metastases were excluded. Complete follow-up was obtained for all patients. MAIN OUTCOME MEASURES: Primary study endpoint was biochemical progression-free survival based on the Phoenix criteria. RESULTS: Seventy-five patients underwent salvage cryotherapy. Mean patient age was 69.3 years. The overall biochemical salvage rate was 50.7% at a median follow-up of 3.9 years. The following factors were independently associated with successful cryotherapy: Precryotherapy Gleason score of 3 + 3 or 3 + 4, low precryotherapy prostate-specific antigen (PSA), low precryotherapy PSA density, longer time to PSA nadir after radiotherapy, and low postcryotherapy PSA nadir. A postcryotherapy PSA nadir of 0.5 ng/mL or less was associated with a biochemical progression-free survival of 79.7% at 3 years and 64.7% at 5 years, whereas a postcryotherapy PSA nadir above 0.5 was associated with a biochemical progression-free survival of 5.6% at 3 years and 0% at 5 years (p < 0.0001). CONCLUSION: Approximately 50% of the patients achieved biochemical salvage with cryoablation at 5 years. Nadir PSA after salvage was the strongest predictor of biochemical progression-free survival in our cohort.

Concurrent Radiotherapy and Triweekly Carboplatin for the Definitive Treatment of Locally Advanced Laryngeal Carcinoma.

PURPOSE OF THE STUDY: In 2003, our institution adopted triweekly carboplatin (tCb) area under the curve (AUC) 5 as an alternative to high-dose cisplatin (100 mg/m) for select patients receiving definitive concurrent chemoradiation for locally advanced laryngeal carcinoma (LALC). Here, we present our experience and outcomes with this definitive concurrent chemoradiation regimen. METHODS: From January 2003 through December 2013, 53 patients with stage III (60%) or IVA (40%) LALC were treated with tCb AUC 5 and concurrent radiotherapy to 70 Gy without neoadjuvant chemotherapy. Reasons for using carboplatin instead of cisplatin in these patients were: age 70 and older (21%), poor renal function (6%), presence of 1 or more major comorbid condition(s) (36%), and per discretion of the treating medical oncologist (38%). Primary disease site was glottis in 22 (42%) patients and supraglottis in 31 (58%) patients. RESULTS: Median follow-up time was 63 months for surviving patients. Out of the 53 patients, 43 (81%) received all 3 cycles of carboplatin and all patients received their intended dose of radiotherapy. Although 17 (32%) patients required a feeding tube during treatment, only 2 (4%) required it long term. There were no acute treatment-related grade 4 or 5 hematologic toxicities. On last follow-up, 14 (26%) patients had died of intercurrent disease. For the subgroup of "RTOG 9111 eligible" patients in our cohort (n=46), 5-year estimates of overall survival, disease-free survival, laryngectomy-free survival, larynx preservation, and locoregional control were: 49%, 42%, 39%, 80%, and 63%, respectively. CONCLUSIONS: In patients with LALC who are suboptimal candidates for high-dose cisplatin, our experience suggests that tCb AUC 5 with concurrent radiotherapy provides acceptable outcomes with tolerable toxicity.

Concurrent Radiotherapy With Cetuximab or Platinum-based Chemotherapy for Locally Advanced Cutaneous Squamous Cell Carcinoma of the Head and Neck.

OBJECTIVES: The management of high-risk cutaneous squamous cell carcinoma of the head and neck (SCCHN) is not well defined. We review outcomes in patients with locally advanced cutaneous SCCHN treated with radiation and concomitant platinum (Pt)-based chemotherapy or cetuximab (Cx). METHODS: We identified 23 patients treated at our institution from 2007 to 2014. Systemic therapy consisted of Pt-based chemotherapy for 15 (65%) patients and Cx for 8 (35%) patients. Treatment intent was definitive for 48% and adjuvant for 52% of the cases. RESULTS: The majority (87%) of patients had stage III/IV disease and 9 (39%) patients had unresectable disease. All patients were being treated for recurrent disease. Aside from median age (59 Pt vs. 71 Cx, P=0.04), there were no significant differences in patient and tumor characteristics between those receiving Pt versus Cx therapy. At mean follow-up of 24 months, locoregional recurrence and distant failure were observed in 52% and 17% of all patients, respectively. Estimated 2-year disease-free survival and overall survival in the Cx versus Pt groups were: 50% versus 30% (P=0.25), and 73% versus 40% (P=0.32), respectively. CONCLUSIONS: Radiotherapy with either concurrent Pt or Cx appears to offer similar clinical outcomes in patients with locally advanced cutaneous SCCHN.

Sequential versus "sandwich" sequencing of adjuvant chemoradiation for the treatment of stage III uterine endometrioid adenocarcinoma.

OBJECTIVE: To compare the efficacy and tolerance of adjuvant chemotherapy and radiotherapy delivered in sequential (chemotherapy followed by radiation) versus "sandwich" fashion (chemotherapy, interval radiation, and remaining chemotherapy) after surgery in patients with FIGO stage III uterine endometrioid adenocarcinoma. METHODS: From 2004 to 2011, we identified 51 patients treated at our institution fitting the above criteria. All patients received surgical staging followed by adjuvant chemoradiation (external-beam radiation therapy (EBRT) with or without high-dose rate (HDR) vaginal brachytherapy (VB)). Of these, 73% and 27% of patients received their adjuvant therapy in sequential and sandwich fashion, respectively. RESULTS: There were no significant differences in clinical or pathologic factors between patients treated with either regimen. Thirty-nine (76%) patients had stage IIIC disease. The majority of patients received 6 cycles of paclitaxel with carboplatin or cisplatin. Median EBRT dose was 45 Gy and 54% of patients received HDR VB boost (median dose 21 Gy). There were no significant differences in the estimated 5-year overall survival, local progression-free survival, and distant metastasis-free survival between the sequential and sandwich groups: 87% vs. 77% (p=0.37), 89% vs. 100% (p=0.21), and 78% vs. 85% (p=0.79), respectively. No grade 3-4 genitourinary or gastrointestinal toxicities were reported in either group. There was a trend towards higher incidence of grade 3-4 hematologic toxicity in the sandwich group. CONCLUSION: Adjuvant chemoradiation for FIGO stage III endometrioid uterine cancer given in either sequential or sandwich fashion appears to offer equally excellent early clinical outcomes and acceptably low toxicity.

Evaluation of two intracavitary high-dose-rate brachytherapy devices for irradiating additional and irregularly shaped volumes of breast tissue.

The SAVI and Contura breast brachytherapy applicators represent 2 recent advancements in brachytherapy technology that have expanded the number of women eligible for accelerated partial breast irradiation in the treatment of early-stage breast cancer. Early clinical experience with these 2 single-entry, multichannel high-dose-rate brachytherapy devices confirms their ease of use and dosimetric versatility. However, current clinical guidelines for SAVI and Contura brachytherapy may result in a smaller or less optimal volume of treated tissue compared with traditional interstitial brachytherapy. This study evaluates the feasibility of using the SAVI and Contura to irradiate larger and irregularly shaped target volumes, approaching what is treatable with the interstitial technique. To investigate whether additional tissue can be treated, 17 patients treated with the SAVI and 3 with the Contura were selected. For each patient, the planning target volume (PTV) was modified to extend 1.1 cm, 1.3 cm, and 1.5 cm beyond the tumor bed cavity. To evaluate dose conformance to an irregularly shaped target volume, 9 patients treated with the SAVI and 3 with the Contura were selected from the original 20 patients. The following asymmetric PTV margin combinations were assessed for each patient: 1.5/0.3, 1.3/0.3, and 1.1/0.3 cm. For all patients, treatment planning was performed, adopting the National Surgical Adjuvant Breast and Bowel Project guidelines, and dosimetric comparisons were made. The 6-1 and 8-1 SAVI devices can theoretically treat a maximal tissue margin of 1.5 cm and an asymmetric PTV with margins ranging from 0.3 to 1.5 cm. The 10-1 SAVI and Contura can treat a maximal margin of 1.3 cm and 1.1 cm, respectively, and asymmetric PTV with margins ranging from 0.3-1.3 cm. Compared with the Contura, the SAVI demonstrated greater dosimetric flexibility. Risk of developing excessive hot spots increased with the size of the SAVI device. Both the SAVI and Contura appear capable of treating >1.0-cm margins and irregularly shaped PTVs. The 6-1 SAVI device demonstrated the greatest versatility in targeting PTVs approaching what is treatable using the interstitial technique.

Population-based study of competing mortality in head and neck cancer.

PURPOSE: Patients with head and neck cancer (HNC) are at high risk of death resulting from noncancer causes and second malignancies (ie, competing mortality). Variation in competing mortality risk complicates individual treatment choices and design and interpretation of clinical studies. METHODS: Using the Surveillance, Epidemiology, and End Results registry, we identified 34,568 patients with nonmetastatic squamous cell carcinoma of the head and neck diagnosed between 1994 and 2003. We developed a multivariable competing-risk regression model to stratify patients according to competing mortality risk and evaluate the impact of this risk on power loss in clinical studies. RESULTS: The 5-year cumulative incidences of all-cause mortality, HNC-specific mortality, and competing mortality were 51.3% (95% CI, 50.8% to 51.9%), 23.8% (95% CI, 23.3% to 24.2%), and 27.6% (95% CI, 26.8% to 28.3%), respectively. Factors associated with increased competing mortality were increasing age, male sex, black race, unmarried status, localized disease, higher socioeconomic status, nonsurgical treatment, and hypopharyngeal, nasopharyngeal, and oral cavity subsites. The 5-year cumulative incidences of competing mortality for patients in low-, medium-, and high-risk score tertiles were 20.0% (95% CI, 18.8% to 21.3%), 27.7% (95% CI, 26.3% to 29.1%), and 33.7% (95% CI, 32.2% to 35.2%), respectively. Compared with patients with low competing mortality risk, relative sample sizes required to show benefit of a treatment regarding all-cause mortality were 12% and 42% higher in the medium- and high-risk groups, respectively. CONCLUSION: Multiple factors affect risk of competing mortality among patients with HNC. Risk stratification would be useful to identify patients most likely to benefit from treatment intensification.

C19orf48 encodes a minor histocompatibility antigen recognized by CD8+ cytotoxic T cells from renal cell carcinoma patients.

PURPOSE: Tumor regression has been observed in some patients with metastatic renal cell carcinoma (RCC) after nonmyeloablative allogeneic hematopoietic cell transplantation (HCT). Cellular and molecular characterization of antigens recognized by tumor-reactive T cells isolated from responding patients could potentially provide insight into the mechanisms of tumor regression. EXPERIMENTAL DESIGN: CD8+ CTL clones that recognized a novel RCC-associated minor histocompatibility (H) antigen presented by HLA-A*0201 were isolated from two patients with metastatic RCC who experienced tumor regression or stable disease following nonmyeloablative allogeneic HCT. These clones were used to screen a cDNA library and isolate the unique cDNA encoding the antigen. RESULTS: An alternative open reading frame in the C19orf48 gene located on chromosome 19q13 encodes the HLA-A*0201-restricted minor H antigen recognized by the RCC-reactive T cells. The differential T-cell recognition of donor- and recipient-derived target cells is attributable to a nonsynonymous single-nucleotide polymorphism within the nucleotide interval that encodes the antigenic peptide. Assays for gene expression and CTL recognition showed that the C19orf48-encoded peptide is widely expressed in renal tumors and solid tumors of other histologies. The antigenic peptide can be processed for CTL recognition via both TAP-dependent and TAP-independent pathways. CONCLUSIONS: Donor T-cell responses against the HLA-A*0201-restricted minor H antigen encoded by C19orf48 may contribute to RCC regression after MHC-matched allogeneic HCT.