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.

Telemedicine for Multidisciplinary Urologic Cancer Care: A Prospective Single Institution Study.

BACKGROUND: We rapidly implemented a telemedicine Multidisciplinary Urologic Cancer Clinic (MDUCC) at the University of Washington/Seattle Cancer Care Alliance during the peak of the COVID-19 Public Health Emergency to maintain our ability to provide multidisciplinary cancer care. We report our experiences though assessment of patient-reported outcomes from our telemedicine MDUCC. METHODS: Video visits with a urologic oncologist, medical oncologist, and radiation oncologist were conducted in the same format as our in-person MDUCC. We prospectively collected patient demographic and clinical data. Patients were invited to complete a post-visit survey that assessed satisfaction, provider trust, travel time, and costs of the telemedicine visit. We estimated travel distances and times from each patient's home to our clinic. RESULTS: Among invited patients, twenty-four patients completed a survey after their telemedicine MDUCC visit. Twenty patients (83%) were at home during the visit. Most (85%) were men, Caucasian (79%), and were being seen in our Bladder Cancer MDUCC (83%). All twenty-four patients responded that they would be willing to have future appointments via telemedicine; eighteen patients (75%) strongly agreed that the encounter was high quality; 19 patients strongly agreed that they were satisfied with their visit. Patients saved an estimated average one-way travel distance of 145 miles and one-way travel time of 179 minutes to convene a telemedicine visit. CONCLUSIONS: Telemedicine MDUCCs are feasible and effective in providing access to multidisciplinary urologic cancer care. Patient satisfaction was high, and many patients were spared a substantial travel burden. Telemedicine may continue to be leveraged to improve access to multidisciplinary urologic cancer care.

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).

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.

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.

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.

Management and Prognosis of Cardiac Metastatic Merkel Cell Carcinoma: A Case-Control Study and Literature Review.

Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin cancer, has a high rate (20%) of distant metastasis. Within a prospective registry of 582 patients with metastatic MCC (mMCC) diagnosed between 2003-2021, we identified 9 (1.5%) patients who developed cardiac metastatic MCC (mMCC). We compared overall survival (OS) between patients with cardiac and non-cardiac metastases in a matched case-control study. Cardiac metastasis was a late event (median 925 days from initial MCC diagnosis). The right heart was predominantly involved (8 of 9; 89%). Among 7 patients treated with immunotherapy, 6 achieved a complete or partial response of the cardiac lesion. Among these 6 responders, 5 received concurrent cardiac radiotherapy (median 20 Gray) with immunotherapy; 4 of 5 did not have local disease progression or recurrence in the treated cardiac lesion. One-year OS was 44%, which was not significantly different from non-cardiac mMCC patients (45%, p = 0.96). Though it occurs relatively late in the disease course, cardiac mMCC responded to immunotherapy and/or radiotherapy and was not associated with worse prognosis compared to mMCC at other anatomic sites. These results are timely as cardiac mMCC may be increasingly encountered in the era of immunotherapy as patients with metastatic MCC live longer.

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.

Performance status (PS) as a predictor of poor response to immune checkpoint inhibitors (ICI) in recurrent/metastatic head and neck cancer (RMHNSCC) patients.

BACKGROUND: Anti-PD1 checkpoint inhibitors (ICI) represent an established standard-of-care for patients with recurrent/metastatic head and neck squamous cell carcinoma (RMHNSCC). Landmark studies excluded patients with ECOG performance status (PS) ≥2; the benefit of ICI in this population is therefore unknown. METHODS: We retrospectively reviewed RMHNSCC patients who received 1+ dose of ICI at our institution between 2013 and 2019. Demographic and clinical data were obtained; the latter included objective response (ORR), toxicity, and any unplanned hospitalization (UH). Associations were explored using uni- and multivariate analysis. Overall survival (OS) was estimated using a Cox proportional hazards model; ORR, toxicity, and UH were evaluated with logistic regression. RESULTS: Of the 152 patients, 29 (19%) had an ECOG PS ≥2. Sixty-six (44%) experienced toxicity; 54 (36%) had a UH. A multivariate model for OS containing PS, smoking status, and HPV status demonstrated a strong association between ECOG ≥2 and shorter OS (p < 0.001; HR = 3.30, CI = 2.01-5.41). An association between OS and former (vs. never) smoking was also seen (p < 0.001; HR = 2.17, CI = 1.41-3.35); current smoking did not reach statistical significance. On univariate analysis, poor PS was associated with inferior ORR (p = 0.03; OR = 0.25, CI = 0.06-0.77) and increased UH (p = 0.04; OR = 2.43, CI = 1.05-5.71). There was no significant association between toxicity and any patient characteristic. CONCLUSIONS: We observed inferior OS, ORR, and rates of UH among ICI-treated RMHNSCC patients with ECOG 2/3. Our findings help frame discussion of therapeutic options in this poor-risk population.

High End-of-Life Health Care Utilization in a Contemporary Cohort of Head and Neck Cancer Patients Treated with Immune Checkpoint Inhibitors.

Background/Objective: End-of-life health care utilization (EOLHCU) is largely uncharacterized among patients with recurrent/metastatic head and neck squamous cell carcinomas (RMHNSCC), particularly now that immune checkpoint inhibitors (ICI) have been introduced to the treatment landscape. We examined this in a single-institution, retrospective study. Design/Settings: We utilized a database of deceased, ICI-treated RMHNSCC patients to obtain demographic and EOLHCU data, the latter of which included advanced care plan documentation (ACPD) and systemic therapy or emergency room (ER)/hospital/intensive care unit (ICU) admission within 30 days of death (DOD). This was compared with a cohort of deceased thoracic malignancy (TM) patients in an exploratory analysis. Multivariate analysis was performed to examine for association between patient factors (such as age, Eastern Cooperative Oncology Group (ECOG) performance status, or smoking status) and overall survival (OS); associations between the said patient factors and EOLHCU were also evaluated. This study was conducted at an academic, tertiary center in the United States. Results: The RMHNSCC patients (n = 74) were more likely to have ACPD (p < 0.01), an emergency department visit (p < 0.01), and/or hospital admission (p < 0.01) within 30 DOD relative to the TM group. There was no difference in ICU admissions, ICU deaths, or systemic therapy at end of life (EOL). The OS declined in association with ECOG performance status (PS) and smoking. No association was observed between patient factors and any EOLHCU metric. Conclusions: At our center, patients with ICI-treated RMHNSCC have higher rates of both ACPD and EOLHCU, suggesting high symptom burden and representing opportunities for further study into supportive care augmentation.

Timing of postoperative radiation therapy and survival in resected salivary gland cancers: Long-term results from a single institution.

OBJECTIVES: Timely administration of postoperative radiation therapy (PORT) impacts oncologic outcomes in resected squamous cell carcinomas of the head and neck. Salivary gland cancers (SGCs) are uncommon, and timing of PORT has not been extensively explored. We aimed to determine if the interval between surgery and PORT impacts outcomes in SGCs. MATERIALS AND METHODS: This is a retrospective study of patients with SGCs who underwent curative intent surgical resection followed by adjuvant PORT. Locoregional recurrence free survival (LRFS), disease free survival (DFS), and overall survival (OS) were estimated using the Kaplan Meier method. A multivariate analysis explored the association between demographics, tumor characteristics, and PORT timing with oncologic outcomes using a stepwise Cox proportional hazards model. RESULTS: 180 eligible patients were identified. The median time to PORT start was 61 (range 8-121) days. 169 (93.5%) of patients received neutron radiation. With a median follow up of 8.2 years in surviving patients, the 10-year OS and LRFS estimates were 61% and 53%. In a multivariate analysis, nodal involvement, histologic grade, and age at diagnosis were associated with OS, while nodal involvement, tumor size, and age at diagnosis were associated with LRFS and DFS. Time to PORT start or completion was not statistically associated with survival outcomes. CONCLUSION: SGC patients who underwent surgery in our tertiary institution received PORT within a median of 61 days after surgery. With long term follow up, PORT timing in this retrospective series was not associated with worse oncologic outcomes, and support timely administration of PORT.

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.