Small Cell Bladder Cancer: Treatment Patterns for Local Disease and Associated Outcomes. A Retrospective Cohort Study.

BACKGROUND: Small cell bladder cancer (SCBC) is a rare histologic subtype with relative paucity of data regarding treatment response and outcomes. We reviewed 2 databases to compare outcomes in patients with localized SCBC treated with cystectomy versus concurrent chemoradiotherapy (CCRT). We hypothesized that survival would be similar with these therapy approaches. METHODS: We retrospectively reviewed our institutional and SEER-Medicare databases to identify patients with SCBC. Overall survival (OS) was determined from the date of diagnosis to last follow-up/death. For those with nonmetastatic disease, a multivariate Cox analysis was used to compare locoregional therapy with neoadjuvant chemotherapy (NAC) + cystectomy versus CCRT. RESULTS: We identified 53 patients in our institutional database and 1166 patients in SEER-Medicare with localized SCBC. Median OS (mOS) with NAC + cystectomy was 46 months (95% CI, 21-72) and 45 months (95% CI, 0-104) in the institutional and SEER-Medicare databases, respectively, whereas mOS with CCRT was 26 months (95% CI, 5-47) and 23 months (95% CI, 18-28) in the 2 series, respectively. In multivariate analysis, NAC followed by cystectomy was associated with an approximately 30% reduction in mortality compared to CCRT in both institutional and national databases but did not reach statistical significance (Institution HR 0.71, 95% CI, 0.22-2.4, P = .58; SEER HR 0.73, 95% CI, 0.49-1.08; P = .11). CONCLUSIONS: SCBC is very aggressive with limited survival observed in our institutional and SEER-Medicare datasets regardless of locoregional therapy used. There is an unmet need to define the optimal locoregional therapy for nonmetastatic stage and identify novel therapeutic targets.

Focal therapy for oligometastatic and oligoprogressive renal cell carcinoma: a narrative review.

Metastatic renal cell carcinoma (RCC) can present with oligometastatic disease and/or develop oligoprogression following systemic therapy. Cytoreductive and focal metastasis-directed therapy options include resection, stereotactic ablative radiation and thermal ablation. Aggressive focal therapy may allow delay in initiation of or modification to systemic therapy and improve clinical outcomes. In this narrative review we synthesize current practice guidelines and prospective data on focal therapy management options and highlight future research. Patient selection and the choice of focal treatment techniques are controversial due to limited and heterogeneous data and patients may benefit from multidisciplinary evaluation. Prospective comparative trials with clearly defined inclusion criteria and relevant end points are needed to clarify the risks and benefits of different approaches.

[Box: see text].

The expanding role of radiation oncology across the prostate cancer continuum.

Radiotherapy is used in the treatment of prostate cancer in a variety of disease states with significant reliance on imaging to guide clinical decision-making and radiation delivery. In the definitive setting, the choice of radiotherapy treatment modality, dose, and fractionation for localized prostate cancer is determined by the patient's initial risk stratification and other clinical considerations. Radiation is also an option as salvage therapy in patients with locoregionally recurrent disease after prior definitive radiation or surgery. In recent years, the role of radiation has expanded for patients with metastatic disease, including prostate-directed radiotherapy in de novo low volume metastatic disease, metastasis-directed therapy for oligorecurrent disease, and palliative management of symptomatic metastases in the advanced setting. Here we review the expanding role of radiation in the treatment of prostate cancer in the definitive, locoregionally recurrent, and metastatic settings, as well as highlight the role of imaging in clinical reasoning, radiation planning, and treatment delivery.

Patterns of chemotherapy use with primary radiotherapy for localized bladder cancer in patients 65 or older.

Introduction: Bladder preservation with concurrent chemoradiotherapy after maximum transurethral resection of bladder tumor is an alternative to radical cystectomy in select patients with muscle invasive bladder cancer (MIBC). Concurrent administration of radio-sensitizing chemotherapy and radiation therapy (RT) has been shown to have superior disease control compared with RT alone and can often be administered with modest added toxicity. We sought to describe national patterns of chemotherapy use. Methods: The linked surveillance, epidemiology, and end results (SEER)-Medicare database was used to identify patients with cT2-4, N0/X, M0/X BC who received radiation between 2004 and 2018. Data on demographics, clinicopathologic factors, therapy and outcomes were extracted. Concurrent utilization of chemotherapy with RT was also identified (CRT). Multivariate logistic regression (MVA) models were used to explore factors associated with receipt of chemotherapy and overall survival (OS). Results: 2190 patients met inclusion criteria. Of these, 850 (38.8%) received no chemotherapy. Among those receiving chemotherapy, the most frequent regimens were single agent carboplatin, cisplatin, or gemcitabine. Factors that were independently associated with decreased likelihood of chemotherapy use were increasing age (OR 0.93, CI 0.92 - 0.95), Hispanic race (compared with White, OR 0.62, CI 0.39 - 0.99), cT3 or T4 (compared with cT2, OR 0.70, CI 0.55 - 0.90), and lower National Cancer Institute comorbidity index (OR 0.60, CI 0.51 - 0.70) (p < 0.05). Variables independently associated with increased likelihood of receipt of chemotherapy were married status (OR 1.28, CI 1.06 - 1.54), higher socioeconomic status (OR 1.31, CI 1.06 - 1.64), and later year of diagnosis (OR 1.09, CI 1.06 - 1.12). Receipt of concurrent chemotherapy with RT was associated with superior OS compared with RT alone. Conclusion: Over a third of patients >/65 years old receiving curative-intent RT for MIBC do not receive concurrent chemotherapy. Considering the improvement in oncologic outcomes with CRT over RT alone and more options, such as low dose gemcitabine which can be administered with modest toxicity, efforts are needed to identify barriers to utilization and increase the use of radio-sensitizing chemotherapy.

Postoperative Radiation Therapy Is Indicated for "Low-Risk" Pathologic Stage I Merkel Cell Carcinoma of the Head and Neck Region but Not for Other Locations.

Purpose: The role of postoperative radiation therapy (PORT) in early stage Merkel cell carcinoma (MCC) is controversial. We analyzed the role of PORT in preventing local recurrences (LR) among patients with low-risk, pathologic stage I MCC based on the location of the primary tumors: head/neck (HN) versus non-HN sites. Methods and Materials: One hundred forty-seven patients with MCC were identified that had "low risk" disease (pathologic T1 primary tumor, negative microscopic margins, negative pathologic node status, no immunosuppression or prior systemic therapy). LR was defined as tumor recurrence within 2 cm of the primary surgical bed, and its frequency was estimated with the cumulative incidence method. Results: Seventy-nine patients received PORT (30 HN, 49 non-HN) with a median dose of 50 Gy (range, 8-64 Gy) and 68 patients were treated with surgery alone (30 HN, 38 non-HN). Overall, PORT was associated with a decreased risk of LR (5-year rate: 0% vs 9.5%; P = .004) with 6 LRs observed in the surgery alone group. Although the addition of PORT significantly reduced LR rates among patients with HN MCC (0% vs. 21%; P = .034), no LRs were observed in patients with non-HN MCC managed with surgery alone. There was no significant difference in MCC-specific survival comparing HN versus non-HN groups, with or without PORT. Conclusions: For low-risk, pathologic stage I MCC of the extremities and trunk, excellent local control rates were achieved with surgery, and PORT is not indicated. However, PORT was associated with a significant reduction in LRs among low-risk MCC of the HN.

Increased risk of recurrence and disease-specific death following delayed postoperative radiation for Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is often treated with surgery and postoperative radiation therapy (PORT). The optimal time to initiate PORT (Time-to-PORT [ttPORT]) is unknown. PURPOSE: We assessed if delays in ttPORT were associated with inferior outcomes. METHODS: Competing risk regression was used to evaluate associations between ttPORT and locoregional recurrence (LRR) for patients with stage I/II MCC in a prospective registry and adjust for covariates. Distant metastasis and death were competing risks. RESULTS: The cohort included 124 patients with median ttPORT of 41 days (range: 8-125 days). Median follow-up was 55 months. 17 (14%) patients experienced a LRR, 14 (82%) of which arose outside the radiation field. LRR at 5 years was increased for ttPORT >8 weeks vs ≤ 8 weeks, 28.0% vs 9.2%, P = .006. There was an increase in the cumulative incidence of MCC-specific death with increasing ttPORT (HR = 1.14 per 1-week increase, P = .016). LIMITATIONS: The relatively low number of LRRs limited the extent of our multivariable analyses. CONCLUSIONS: Delay of PORT was associated with increased LRR, usually beyond the radiation field. This is consistent with the tendency of MCC to spread quickly via lymphatics. Initiation of PORT within 8 weeks was associated with improved locoregional control and MCC-specific survival.

Effects of tissue heterogeneity and comparisons of collapsed cone and Monte Carlo fast neutron patient dosimetry using the University of Washington clinical neutron therapy system (CNTS).

Fast neutron therapy is a high linear energy transfer (LET) radiation treatment modality offering advantages over low LET radiations. Multileaf collimator technology reduces normal-tissue dose (toxicity) and makes neutron therapy more comparable to MV x-ray treatments. Published clinical-trial and other experiences with fast neutron therapy are reported. Early comparative studies failed to consider differences in target-dose spatial conformality between x-ray and neutron treatments, which is especially important for organs-at-risk close to tumor targets. Treatments planning systems (TPS) for high-energy neutrons lag behind TPS tools for MV x-rays, creating challenges for comparative studies of clinical outcomes. A previously published Monte Carlo model of the University of Washington (UW) Clinical Neutron Therapy System (CNTS) is refined and integrated with the RayStation TPS as an external dose planning/verification tool. The collapsed cone (CC) dose calculations in the TPS are based on measured dose profiles and output factors in water, with the absolute dose determined using a tissue-equivalent ionization chamber. For comparison, independent (external) Monte Carlo simulation computes dose on a voxel-by-voxel basis using an atlas that maps Hounsfield Unit (HU) numbers to elemental composition and density. Although the CC algorithm in the TPS accurately computes neutron dose to water compared to Monte Carlo calculations, calculated dose to water differs from bone or tissue depending largely on hydrogen content. Therefore, the elemental composition of tissue and bone, rather than the material or electron density, affects fast neutron dose. While the CC algorithm suffices for reproducible patient dosimetry in fast neutron therapy, adopting methods that consider tissue heterogeneity would enhance patient-specific neutron dose accuracy relative to national standards for other types of ionizing radiation. Corrections for tissue composition have a significant impact on absolute dose and the relative biological effectiveness (RBE) of neutron treatments compared to other radiation types (MV x-rays, protons, and carbon ions).

Radiation therapy for low- and high-risk perineural invasion in head and neck cutaneous squamous cell carcinoma: Clinical outcomes and patterns of failure.

BACKGROUND: Perineural invasion (PNI) in head and neck squamous cell carcinoma (HNSCC) portends poor prognosis. Extent of treatment of nerve pathways with varying degrees of PNI and patterns of failure following elective neural radiotherapy (RT) remain unclear. METHODS: Retrospective review of HNSCC patients with high-risk (clinical/gross, large-nerve, extensive) or low-risk (microscopic/focal) PNI who underwent curative-intent treatment from 2010 to 2021. RESULTS: Forty-four patients (mean follow-up 22 months; 59% high-risk, 41% low-risk PNI) were included. Recurrence following definitive treatment occurred in 31% high-risk and 17% low-risk PNI patients. Among high-risk patients, 69% underwent surgery with post-operative RT and 46% underwent elective neural RT. Local control (83% low-risk vs. 75% high-risk), disease-free, and overall survival did not differ between groups. CONCLUSIONS: High local control rates were achieved in high-risk PNI patients treated with adjuvant or primary RT, including treatment of both involved and uninvolved, communicating cranial nerves, with few failures in electively treated regions.

The Judicious Use of Stereotactic Ablative Radiotherapy in the Primary Management of Localized Renal Cell Carcinoma.

Localized renal cell carcinoma is primarily managed surgically, but this disease commonly presents in highly comorbid patients who are poor operative candidates. Less invasive techniques, such as cryoablation and radiofrequency ablation, are effective, but require percutaneous or laparoscopic access, while generally being limited to cT1a tumors without proximity to the renal pelvis or ureter. Active surveillance is another management option for small renal masses, but many patients desire treatment or are poor candidates for active surveillance. For poor surgical candidates, a growing body of evidence supports stereotactic ablative radiotherapy (SABR) as a safe and effective non-invasive treatment modality. For example, a recent multi-institution individual patient data meta-analysis of 190 patients managed with SABR estimated a 5.5% five-year cumulative incidence of local failure with one patient experiencing grade 4 toxicity, and no other grade ≥3 toxic events. Here, we discuss the recent developments in SABR for the management of localized renal cell carcinoma, highlighting key concepts of appropriate patient selection, treatment design, treatment delivery, and response assessment.

Peripheral lymphocytes and lactate dehydrogenase correlate with response and survival in head and neck cancers treated with immune checkpoint inhibitors.

BACKGROUND: Little is known regarding associations between peripheral blood biomarkers (PBBMs) and survival, response, and toxicity in recurrent/metastatic head and neck squamous cell carcinomas (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs). METHODS: In this single-institution retrospective cohort study, a dataset of patients with R/M HNSCC treated with ICIs between 08/2012-03/2021 was established, including demographic and clinicopathologic characteristics. Pretreatment PBBMs were collected and evaluated for associations with grade ≥3 adverse events (G ≥ 3AE) by CTCAEv5, objective response (ORR) by RECIST 1.1, overall survival (OS), and progression-free survival (PFS). Multivariable models for each outcome were created using elastic net variable selection. RESULTS: Our study included 186 patients, with 51 (27%) demonstrating complete or partial response to immunotherapy. Multivariable models adjusted for ECOG performance status (PS), p16, and smoking demonstrated that pretreatment higher LDH and absolute neutrophils, as well as lower percent lymphocytes correlated with worse OS and PFS. Higher LDH and lower % lymphocytes also correlated with worse ORR. CONCLUSIONS: In the largest study to date examining PBBMs in ICI-treated R/M HNSCCs, our variable selection method revealed PBBMs prognostic for survival and response to immunotherapy. These biomarkers warrant further investigation in a prospective study along with validation with CPS biomarker.

Prostate and metastasis-directed focal therapy in prostate cancer: hype or hope?

INTRODUCTION: The paradigm of focal therapy's role in metastatic patients is being challenged by evolving attitudes and emerging data. At the current time, specifically regarding prostate cancer, does the evidence indicate this is more hype or hope? AREAS COVERED: We searched the literature via PubMed, MEDLINE, and Embase for studies from 2014 to the present addressing focal therapy with non-palliative intent in metastatic prostate cancer patients, emphasizing prospective trials when available. We sought to address all common clinical scenarios: de novo synchronous diagnosis, oligorecurrence, oligoprogression, and mCRPC disease. EXPERT OPINION: Current evidence is strongest, and in our opinion practice-changing, for prostate-directed RT in de novo metastatic patients with low metastatic burden. Metastasis-directed therapy with SBRT is consistently shown to have low rates of toxicity, and promising rates of ADT-free survival and progression-free survival. These can be utilized on a patient-by-patient basis with these endpoints in mind, but do not yet show sufficient benefit to be standard of care. This is a rich area of ongoing research, and many trials should publish in the coming years to shed light on many unanswered questions, including the role of cytoreductive prostatectomy, systemic therapy combined with MDT, and the integration of modern PET imaging.

Neutrophil to lymphocyte ratio and peripheral blood biomarkers correlate with survival outcomes but not response among head and neck and salivary cancer treated with pembrolizumab and vorinostat.

BACKGROUND: Associations between peripheral blood biomarkers and oncologic outcomes were explored in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HN) and salivary gland cancer (SGC) treated with pembrolizumab and vorinostat on a phase II trial (NCT02538510). EXPERIMENTAL DESIGN: Twenty-five HN and 25 SGCs were treated with pembrolizumab and vorinostat. Baseline peripheral blood was available in 21 HN and 20 SGCs and evaluated for associations with grade ≥3 adverse events (G ≥ 3AE) by CTCAEv4, objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). RESULTS: Higher pretreatment neutrophil-to-lymphocyte ratio (NLR) and neutrophils, as well as lower pretreatment lymphocytes and T helper cells correlated with worse OS and PFS. Higher NLR further predicted increased rates of G ≥ 3AEs. No correlations with ORR were observed. CONCLUSIONS: In a prospectively evaluated cohort of HN and SGCs treated with pembrolizumab and vorinostat, we observed novel associations between peripheral blood biomarkers and oncologic outcomes and toxicities.

A Prospective Study of a Resorbable Intravesical Fiducial Marker for Bladder Cancer Radiation Therapy.

Purpose: We conducted a prospective pilot study to evaluate safety and feasibility of TraceIT, a resorbable radiopaque hydrogel, to improve image guidance for bladder cancer radiation therapy (RT). Methods and Materials: Patients with muscle invasive bladder cancer receiving definitive RT were eligible. TraceIT was injected intravesically around the tumor bed during maximal transurethral resection of bladder tumor. The primary endpoint was the difference between radiation treatment planning margin on daily cone beam computed tomography based on alignment to TraceIT versus standard-of-care pelvic bone anatomy. The Van Herk margin formula was used to determine the optimal planning target volume margin. TraceIT visibility, recurrence rates, and survival were estimated by Kaplan-Meier method. Toxicity was measured by Common Terminology Criteria for Adverse Events version 4.03. Results: The trial was fully accrued and 15 patients were analyzed. TraceIT was injected in 4 sites/patient (range, 4-6). Overall, 94% (95% confidence interval [CI], 90%-98%) of injection sites were radiographically visible at RT initiation versus 71% (95% CI, 62%-81%) at RT completion. The median duration of radiographic visibility for injection sites was 106 days (95% CI, 104-113). Most patients were treated with a standard split-course approach with initial pelvic radiation fields, then midcourse repeat transurethral resection of bladder tumor followed by bladder tumor bed boost fields, and 14/15 received concurrent chemotherapy. Alignment to fiducials could allow for reduced planning target volume margins (0.67 vs 1.56 cm) for the initial phase of RT, but not for the boost (1.01 vs 0.96 cm). This allowed for improved target coverage (D95% 80%-83% to 91%-94%) for 2 patients retrospectively planned with both volumetric-modulated arc therapy and 3-dimensional conformal RT. At median follow-up of 22 months, no acute or late complications attributable to TraceIT placement occurred. No patients required salvage cystectomy. Conclusions: TraceIT intravesical fiducial placement is safe and feasible and may facilitate tumor bed delineation and targeting in patients undergoing RT for localized muscle invasive bladder cancer. Improved image guided treatment may facilitate strategies to improve local control and minimize toxicity.

Consensus Statement on Proton Therapy for Prostate Cancer.

Proton therapy is a promising but controversial treatment in the management of prostate cancer. Despite its dosimetric advantages when compared with photon radiation therapy, its increased cost to patients and insurers has raised questions regarding its value. Multiple prospective and retrospective studies have been published documenting the efficacy and safety of proton therapy for patients with localized prostate cancer and for patients requiring adjuvant or salvage pelvic radiation after surgery. The Particle Therapy Co-Operative Group (PTCOG) Genitourinary Subcommittee intends to address current proton therapy indications, advantages, disadvantages, and cost effectiveness. We will also discuss the current landscape of clinical trials. This consensus report can be used to guide clinical practice and research directions.

Intensity-Modulated Proton Therapy for Nasopharynx Cancer: 2-year Outcomes from a Single Institution.

PURPOSE: Advances in radiotherapy have improved tumor control and reduced toxicity in the management of nasopharyngeal carcinoma (NPC). Local failure remains a problem for some patients with advanced primary tumors, and toxicities are significant given the large treatment volume and tumor proximity to critical structures, even with modern photon-based radiotherapy. Proton therapy has unique dosimetric advantages, and recent technological advances now allow delivery of intensity-modulated proton therapy (IMPT), which can potentially improve the therapeutic ratio in NPC. We report our 2-year clinical outcomes with IMPT for NPC. MATERIALS AND METHODS: We retrospectively reviewed treatment records of patients with NPC treated with IMPT at our center. Demographics, dosimetry, tumor response, local regional control (LRC), distant metastasis, overall survival, and acute and late toxicity outcomes were reviewed. Analyses were performed with descriptive statistics and Kaplan-Meier method. Toxicity was graded per Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: Twenty-six patients were treated from 2015 to 2020. Median age was 48 years (range, 19-73 years), 62% (n = 16) had T3-T4 disease, 92% (n = 24) were node positive, 92% (n = 24) had stage III-IV disease, and 69% (n = 18) had positive results for Epstein-Barr virus. Dose-painted pencil-beam IMPT was used. Most patients (85%; 22 of 26) were treated with 70 Gy(RBE) in 33 fractions once daily; 4 (15%) underwent hyperfractionated accelerated treatment twice daily. All received concurrent cisplatin chemotherapy; 7 (27%) also received induction chemotherapy. All patients (100%) completed the planned radiotherapy, and no acute or late grade 4 or 5 toxicities were observed. At median follow-up of 25 months (range, 4-60), there were 2 local regional failures (8%) and 3 distant metastases (12%). The Kaplan-Meier 2-year LRC, freedom from distant metastasis, and overall survival were 92%, 87%, and 85% respectively. CONCLUSION: IMPT is feasible in locally advanced NPC with early outcomes demonstrating excellent LRC and favorable toxicity profile. Our data add to the growing body of evidence supporting the clinical use of IMPT for NPC.

Comparisons of 3-Dimensional Conformal and Intensity-Modulated Neutron Therapy for Head and Neck Cancers.

PURPOSE: Neutron therapy is a high linear energy transfer modality that is useful for the treatment of radioresistant head and neck (H&N) cancers. It has been limited to 3-dimensioanal conformal-based fast-neutron therapy (3DCNT), but recent technical advances have enabled the clinical implementation of intensity-modulated neutron therapy (IMNT). This study evaluated the comparative dosimetry of IMNT and 3DCNT plans for the treatment of H&N cancers. MATERIALS AND METHODS: Seven H&N IMNT plans were retrospectively created for patients previously treated with 3DCNT at the University of Washington (Seattle). A custom RayStation model with neutron-specific scattering kernels was used for inverse planning. Organ-at-risk (OAR) objectives from the original 3DCNT plan were initially used and were then systematically reduced to investigate the feasibility of improving a therapeutic ratio, defined as the ratio of the mean tumor to OAR dose. The IMNT and 3DCNT plan quality was evaluated using the therapeutic ratio, isodose contours, and dose volume histograms. RESULTS: When compared with the 3DCNT plans, IMNT reduces the OAR dose for the equivalent tumor coverage. Moreover, IMNT is most advantageous for OARs in close spatial proximity to the target. For the 7 patients with H&N cancers examined, the therapeutic ratio for IMNT increased by an average of 56% when compared with the 3DCNT. The maximum OAR dose was reduced by an average of 20.5% and 20.7% for the spinal cord and temporal lobe, respectively. The mean dose to the larynx decreased by an average of 80%. CONCLUSION: The IMNT significantly decreases the OAR doses compared with 3DCNT and provides comparable tumor coverage. Improvements in the therapeutic ratio with IMNT are especially significant for dose-limiting OARs near tumor targets. Moreover, IMNT provides superior sparing of healthy tissues and creates significant new opportunities to improve the care of patients with H&N cancers treated with neutron therapy.

Postoperative, Single-Fraction Radiation Therapy in Merkel Cell Carcinoma of the Head and Neck.

PURPOSE: Conventionally fractionated, postoperative radiation therapy (cPORT; 50 Gy in 25 fractions) is considered for patients with Merkel cell carcinoma (MCC) to improve locoregional control. However, cPORT is associated with acute toxicity, especially in the head and neck (H&N) region, and requires daily treatments over several weeks. We previously reported high rates of durable local control with minimal toxicity using 8-Gy single-fraction radiation therapy (SFRT) in the metastatic setting. We report early results on a cohort of patients with localized H&N MCC who received postoperative SFRT if a cPORT regimen was not feasible. METHODS AND MATERIALS: Twelve patients with localized MCC of the H&N (clinical/pathologic stages I-II) and no prior radiation therapy to the region were identified from an institutional review board-approved prospective registry who underwent surgical resection followed by postoperative SFRT. Time to event was calculated starting from the date of resection before SFRT. The cumulative incidence of in-field locoregional recurrences and out-of-field recurrences was estimated with death as a competing risk. RESULTS: Twelve patients with H&N MCC were identified with clinical/pathologic stages I-II H&N MCC. Median age at diagnosis was 81 years (range, 58-96 years); 25% had immunosuppression. At a median follow-up of 19 months (range, 8-34), there were no in-field locoregional recurrences. A single out-of-field regional recurrence was observed, which was successfully salvaged. There were no MCC-specific deaths. No radiation-associated toxicities greater than grade 1 (Common Terminology Criteria for Adverse Events v5) were observed. CONCLUSIONS: Preliminary data suggest that SFRT could offer a potential alternative to cPORT to treat the primary site for localized H&N MCC, particularly in elderly or frail patients, with promising in-field local control and minimal toxicity. Further data with validation in larger cohorts are needed to confirm the sustained safety and efficacy of postoperative SFRT.

Proton Therapy for Locally Advanced Oropharyngeal Cancer: Initial Clinical Experience at the University of Washington.

PURPOSE: Proton therapy can potentially improve the therapeutic ratio over conventional radiation therapy for oropharyngeal squamous cell cancer (OPSCC) by decreasing acute and late toxicity. We report our early clinical experience with intensity-modulated proton therapy (IMPT). MATERIALS AND METHODS: We retrospectively reviewed patients with OPSCC treated with IMPT at our center. Endpoints include local regional control (LRC), progression-free survival (PFS), overall survival (OS), tumor response, and toxicity outcomes. Toxicity was graded as per the Common Terminology Criteria for Adverse Events v4.03. Descriptive statistics and Kaplan-Meier method were used. RESULTS: We treated 46 patients from March 2015 to August 2017. Median age was 58 years, 93.5% were male, 67% were nonsmokers, 98% had stage III-IVB disease per the 7th edition of the AJCC [American Joint Committee on Cancer] Cancer Staging Manual, and 89% were p16 positive. Twenty-eight patients received definitive IMPT to total dose of 70 to 74.4 Gy(RBE), and 18 patients received postoperative IMPT to 60 to 66 Gy(RBE) following transoral robotic surgery (TORS). Sixty-four percent of patients received concurrent systemic therapy. There were no treatment interruptions or observed acute grade 4 or 5 toxicities. Eighteen patients had percutaneous endoscopic gastrostomy (PEG) tube placement; the majority (14) were placed prophylactically. The most common grade 3 acute toxicities were dermatitis (76%) and mucositis (72%). The most common late toxicity was grade 2 xerostomia (30%). At a median follow-up time of 19.2 months (interquartile range [IQR], 11.2-28.4), primary complete response was 100% and nodal complete response was 92%. One patient required a salvage neck dissection owing to an incomplete response at 4 months. There were no recorded local regional or marginal recurrences, PFS was 93.5%, and OS was 95.7%. CONCLUSION: Our early results for IMPT in OPSCC are promising with no local regional or marginal recurrences and a favorable toxicity profile. Our data add to a body of evidence that supports the clinical use of IMPT. Randomized comparative trials are encouraged.

Rectal Hydrogel Spacer Improves Late Gastrointestinal Toxicity Compared to Rectal Balloon Immobilization After Proton Beam Radiation Therapy for Localized Prostate Cancer: A Retrospective Observational Study.

PURPOSE: Our purpose was to compare dosimetric parameters and late gastrointestinal outcomes between patients treated with proton beam therapy (PBT) for localized prostate cancer with rectal balloon immobilization versus a hydrogel rectal spacer. METHODS AND MATERIALS: Patients with localized, clinical stage T1-4 prostate adenocarcinoma were treated at a single institution using conventionally fractionated, dose-escalated PBT from 2013 to 2018. Patient-reported gastrointestinal toxicity was prospectively collected, and the incidence of rectal bleeding was retrospectively reviewed from patient records. RESULTS: One hundred ninety-two patients were treated with rectal balloon immobilization, and 75 were treated with a rectal spacer. Rectal hydrogel spacer significantly improved rectal dosimetry while maintaining excellent target coverage. The 2-year actuarial rate of grade 2+ late rectal bleeding was 19% and 3% in the rectal balloon and hydrogel spacer groups, respectively (P = .003). In univariable analysis, the probability of grade 2+ rectal bleeding was significantly correlated with increasing rectal dose. In multivariable analysis, only receipt of spacer hydrogel (hazard ratio, 0.145; P = .010) and anticoagulation use (hazard ratio, 5.019; P < .001) were significantly associated with grade 2+ bleeding. At 2-year follow-up, patient-reported Expanded Prostate Cancer Index Composite bowel quality of life composite scores were less diminished in the hydrogel spacer group (absolute mean difference, 5.5; P = .030). CONCLUSIONS: Use of rectal hydrogel spacer for prostate PBT is associated with a significantly lower incidence of clinically relevant, late rectal bleeding and lower decrement in long-term, patient-reported bowel quality of life compared with rectal balloon immobilization. Our results suggest that hydrogel spacer may improve rectal sparing compared with rectal balloon immobilization during PBT for prostate cancer.

Chemotherapy in Esthesioneuroblastoma/Olfactory Neuroblastoma: An Analysis of the Surveillance Epidemiology and End Results (SEER) 1973-2015 Database.

OBJECTIVE: Chemotherapy has been proposed as an adjunct to primary local therapy in esthesioneuroblastoma (ENB)/olfactory neuroblastoma (ON), but its role has not been precisely defined. Here, we evaluated its role in ENB treatment. MATERIALS AND METHODS: The Surveillance Epidemiology and End Results (SEER) database was queried for ENB/ON (International Classification of Diseases-3 9522). Cases met criteria for inclusion if they were unique, had a primary location in the nasal cavity, and had adequate information for Kadish staging derivation. Univariable and multivariable Cox analyses assessed chemotherapy treatment effect on disease-specific survival (DSS) and overall survival (OS). Multiple imputation addressed missing data. A P<0.05 was designated for statistical significance. RESULTS: In adjusted multivariable analyses, chemotherapy treatment was associated with inferior DSS (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.21-2.51; P=0.003) and OS (HR, 1.71; 95% CI, 1.26-2.32; P=0.001). Among the subset with local or regional disease treated with surgery and/or radiation therapy, chemotherapy remained associated with inferior outcomes DSS (HR, 2.78; 95% CI, 1.63-4.74; P<0.001) and OS (HR, 2.18; 95% CI, 1.45-3.27; P<0.001). Chemotherapy treatment misclassification did not explain these findings. CONCLUSIONS: This analysis does not support chemotherapy to improve either DSS or OS in primary ENB/ON treatment, after controlling for known ENB prognostic factors available from SEER. Other prognostic and treatment selection factors could exist which were not controlled in these analyses. Chemotherapy could beneficially affect outcomes other than DSS or OS. Although the concerns have been expressed regarding chemotherapy treatment misclassification in SEER, their analyses did not identify such misclassification as an explanation for our findings.