Search

The purpose of this critical review is to provide an overview of the role and outcomes associated with the use of local therapy for patients with oligometastatic gastrointestinal cancers.A review of clinical data was performed to describe outcomes associated with the use of systemic therapy and/or locoregional therapies for patients with oligometastatic gastrointestinal cancers including esophagus, gastric, liver, biliary, pancreas, colorectal, and anal canal.This review describes outcomes associated with current first line systemic therapy and oligometastasis directed locoregional therapy for patients with gastrointestinal cancers. Available data suggest that for well-selected patients among each gastrointestinal disease subsite, the use of local therapy is associated with favorable disease control and possible survival benefit.These data emphasize the importance of multidisciplinary collaboration and consideration of radiation therapy for patients with oligometastatic gastrointestinal cancers to improve locoregional control and progression-free survival. Multiple trials are ongoing to determine whether metastasis-directed radiation therapy improves overall survival.

The purpose of this work was to describe pancreatic ductal adenocarcinoma (PDAC) patterns of locoregional spread and recurrence to help guide clinicians on (neo)adjuvant radiation therapy (RT) planning strategies and target volume delineation.A comprehensive review of clinical data was performed to describe PDAC patterns of locoregional spread, including extrapancreatic tumor extension, perineural invasion, regional lymph node involvement, and patterns of disease recurrence as influenced by (neo)adjuvant treatment strategy.This review describes PDAC patterns of spread, disease progression, and evolving treatment techniques. Based upon this data, we advocate for inclusion of elective at-risk regions of extrapancreatic extension, perineural invasion, and lymphatic spread for patients receiving neoadjuvant RT.This review provides a nuanced description of PDAC patterns of spread and recurrence to guide clinicians on target volume delineation and planning strategies to maximize the effectiveness of neo(adjuvant) RT delivery for patients with PDAC. Further prospective studies are needed to better define the optimal RT dose, fractionation regimens, and target volumes to be used in the (neo)adjuvant setting.

Chemotherapy followed by margin-negative resection (R0) is the treatment of choice for patients with localized pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant multiagent chemotherapy (MAC) or MAC then radiotherapy (RT) may optimize surgical candidacy. The purpose of this study was to compare pathologic outcomes of MAC followed by conventionally fractionated radiotherapy (CRT) versus stereotactic body radiotherapy (SBRT) for patients with resected PDAC.Patients diagnosed with nonmetastatic PDAC between 2012 and 2017 and who received preoperative MAC or MAC+RT were identified in the National Cancer Database. Variables associated with R0 and overall survival were identified with logistic regression and Cox analysis (P0.05).A total of 5273 patients were identified (MAC: 3900, MAC+CRT: 955, MAC+SBRT: 418). The median RT dose/fraction (fx) in the MAC+CRT and MAC+SBRT cohorts was 50.4 Gy/28 fx and 33 Gy/5 fx. Patients receiving MAC+CRT versus MAC+SBRT had similar rates of ypT3-T4 disease (54% vs. 58%, P=0.187), R0 (87% vs. 84%, P=0.168), and pathologic complete response (pathologic complete response; 6% vs. 4%, P=0.052), however, MAC+CRT was associated with less regional lymphatic disease (ypN+: 28% vs. 41%, P0.001). The median overall survival of patients receiving MAC+CRT versus MAC+SBRT was 24.6 versus 29.5 months (P=0.045).For patients with resected PDAC, MAC+CRT, and MAC+SBRT had similar rates of R0 and pathologic complete response, although MAC+CRT was associated with lower ypN+. Prospective evaluation of neoadjuvant RT regimens with attention to radiation therapy design is warranted.

No standard treatment paradigm exists for previously irradiated locally recurrent rectal cancer (PILRRC). Carbon-ion radiotherapy (CIRT) may improve oncologic outcomes and reduce toxicity compared with combined modality therapy (CMT). Eighty-five patients treated at Institution A with CIRT alone (70.4 Gy/16 fx) and eighty-six at Institution B with CMT (30 Gy/15 fx chemoradiation, resection, intraoperative electron radiotherapy (IOERT)) between 2006 and 2019 were retrospectively compared. Overall survival (OS), pelvic re-recurrence (PR), distant metastasis (DM), or any disease progression (DP) were analyzed with the Kaplan–Meier model, with outcomes compared using the Cox proportional hazards model. Acute and late toxicities were compared, as was the 2-year cost. The median time to follow-up or death was 6.5 years. Median OS in the CIRT and CMT cohorts were 4.5 and 2.6 years, respectively (p ≤ 0.01). No difference was seen in the cumulative incidence of PR (p = 0.17), DM (p = 0.39), or DP (p = 0.19). Lower acute grade ≥ 2 skin and GI/GU toxicity and lower late grade ≥ 2 GU toxicities were associated with CIRT. Higher 2-year cumulative costs were associated with CMT. Oncologic outcomes were similar for patients treated with CIRT or CMT, although patient morbidity and cost were lower with CIRT, and CIRT was associated with longer OS. Prospective comparative studies are needed.

The purpose of our study is to determine the rate of detectability of ctHPVDNA after surgery but before adjuvant therapy in patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV[+]OPSCC) and to investigate whether detectable ctHPVDNA at this time point may be associated with risk of recurrence.We examined prospectively collected samples from patients with OPSCC in a blinded fashion using a multianalyte polymerase chain reaction assay. We collected 45 samples from patients with HPV(+)OPSCC preop (before any treatment) and 159 samples postop (before or at the start of adjuvant radiation therapy). We identified samples via the radiation oncology biobank or via participation in a clinical trial. Radiation therapy consisted of 60 Gy ± cisplatin or de-escalation (30 Gy to 36 Gy in 20 bid fractions + docetaxel). For our preliminary analysis, 32 patients had paired samples available pre- and postop. We performed additional exploratory analyses including associations of patient and tumor characteristics with recurrence using Cox proportional hazards models for all 159 postop samples. We compared detectability of ctHPVDNA across groups using logistic regression. We used Kaplan-Meier to estimate recurrence-free survival.In a paired analysis of 32 pre- and postop timepoints, 94% of patients had detectable ctHPVDNA preop and 41% did postop. Recurrence-free survival at 18 months was 83% (95% confidence interval, 47%-95%) for patients with detectable postop ctHPVDNA compared with 100% for patients with undetectable postop ctHPVDNA (P = .094). In an exploratory analysis of nonpaired postop samples, ctHPVDNA was detectable in 26% of patients (41 of 159) (median of 22 days postop). Age (odds ratio,1.06, P = .025), lymphovascular space invasion (odds ratio, 3.17, P = .011) and extranodal extension (odds ratio = 5.67, P = .001) were associated with detectable ctHPVDNA after surgery. Detectable postop ctHPVDNA was significantly associated with recurrence-free survival (P.001).Among patients with detectable preop ctHPVDNA, a significant proportion have detectable postop ctHPVDNA in paired postop samples collected before the initiation of adjuvant radiation therapy. Future prospective study is warranted to investigate the association of detectable postop ctHPVDNA with recurrence, including in comparison to established clinical and pathologic risk factors.

Anal canal and peri-anal squamous cell carcinomas (ASCCs) are relatively rare cancers that affect approximately 8000 patients per year in the United States [...]

Background Increased risk of a second primary malignancy (SPM) before or after diagnosis of anal squamous cell carcinoma (ASCC) has been reported in a previous single‐institution study. We hypothesize that patients diagnosed with ASCC are at increased risk for developing SPMs before or after the diagnosis of ASCC. The primary objective of this study was to identify the diagnoses of cancer most likely to occur as SPMs before or after ASCC. Methods This work employs the Surveillance, Epidemiology, and End Results (SEER) Program registry data to conduct a US‐population‐based study of patients diagnosed with ASCC between 1975 and 2016. In patients diagnosed with ASCC, we evaluated the risk of SPMs and the risk of developing ASCC as an SPM after another cancer using standardized incidence ratios (SIR) for all SPMs by calculating the ratio of observed events in the ASCC cohort compared to expected (O/E) events in a matched reference cohort of the general population. Results A total of 7,594 patients with primary ASCC were included. Patients with ASCC were at increased risk of the diagnosis of an SPM (SIR = 1.45), particularly cancers of the lung, vulva, oropharynx, or colon. Patients with ASCC had an increased rate of previous malignancy (SIR = 1.23), especially Kaposi sarcoma or vulvar cancer. Overall elevated incidence of SPMs was unrelated to prior radiation treatment. Radiation treatment was associated with increased risk for SPMs in the female genital system but appeared protective against prostate cancer as SPMs. Conclusions Our findings support increased surveillance and screening for second malignancies in patients with these diagnoses, as patients with ASCC are often either survivors of a prior cancer diagnosis or are at increased risk of developing later malignancies., Survivors of anal squamous cell carcinoma are at increased risk for particular second malignancies and should be screened for these. Risk of second malignancies is sometimes related to radiation therapy, but radiation can also be protective against second cancers in some cases.

Purpose Our purpose was to determine the effect of chemoradiotherapy (CRT) on patient-reported quality of life (QOL) for patients with intact pancreas cancer. Methods and Materials We reviewed a prospective QOL registry for patients with intact, clinically localized pancreatic ductal adenocarcinoma treated with CRT between June 2015 and November 2018. QOL was assessed pre-CRT (immediately before CRT, after neoadjuvant chemotherapy) and at the completion of CRT with the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) and its component parts: FACT-General (FACT-G) and hepatobiliary cancer subscore (HCS). A minimally important difference from pre-CRT was defined as ≥ 6, 5, and 8 points for FACT-G, HCS, and FACT-Hep, respectively. Results Of 157 patients who underwent CRT, 100 completed both pre- and post-CRT surveys and were included in the primary analysis. Median age at diagnosis was 65 years (range, 23-90). National Comprehensive Cancer Network resectability status was resectable (3%), borderline resectable (40%), or locally advanced (57%). Folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) (75%) or gemcitabine and nab-paclitaxel (42%) were given for a median of 6 cycles (range, 0-42) before CRT. Radiation therapy techniques included 3-dimensional conformal (22%), intensity modulated photon (55%), and intensity modulated proton (23%) radiation therapy to a median dose of 50 Gy (range, 36-62.5). Concurrent chemotherapy was most commonly capecitabine (82%). Sixty-three patients (63%) had surgery after CRT. The mean decline in FACT-G, HCS subscale, and FACT-Hep from pre- to post-CRT was 3.5 (standard deviation [SD], 13.7), 1.7 (SD 7.8), and 5.2 (SD 19.4), respectively. Each of these changes were statistically significant, but did not meet the minimally important difference threshold. Pancreatic head tumor location was associated with decline in FACT-Hep. Nausea was the toxicity with the greatest increase from pre- to post-CRT by both physician-assessment and patient-reported QOL. Conclusions For patients with intact pancreatic adenocarcinoma, modern CRT is well tolerated with minimal decline in QOL during treatment.

Radiation therapy and systemic therapy are the primary non-surgical treatment modalities for head and neck squamous cell carcinoma (HNSCC). Despite advances in our biologic understanding of this disease and the development of novel therapeutics, treatment resistance remains a significant problem. It has become increasingly evident that the innate and adaptive immune systems play a significant role in the modulation of anti-tumor responses to traditional cancer-directed therapies. By inducing DNA damage and cell death, radiation therapy appears to activate both innate and adaptive immune responses. Immunotherapies targeting programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) also have yielded promising results, particularly in the recurrent/metastatic setting. In this review, we will discuss the rationale for combining radiotherapy with immunotherapy to harness the immunomodulatory effects of radiation therapy on HNSCC, as well as biomarkers for immune response. We will also review recent preclinical and clinical data exploring these combinations in various contexts, including recurrent/metastatic and locally advanced disease. Among those with locally advanced HNSCC, we will discuss clinical trials employing immunotherapy either concurrently with radiation therapy or as maintenance following chemoradiation in both the definitive and postoperative settings, with or without the use of cisplatin-based or non-cisplatin-based chemotherapy.

BACKGROUND: Although surgical resection is the preferred curative-intent treatment option for patients with non-metastatic, extra-hepatic biliary cancer (EBC), radiotherapy (RT) or chemoradiotherapy (CRT) may be utilized in select cases when surgical resection is not feasible. The purpose of this study is to report the efficacy and adverse events (AEs) associated with CRT for patients with locally advanced and unresectable EBC. METHODS: This was a retrospective cohort study of patients with EBC, including extra-hepatic cholangiocarcinoma or gallbladder cancer, deemed inoperable who received RT between 1998 and 2018. The median RT dose was 50.4 Gy in 28 fractions and 94% received concurrent 5-fluorouracil. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS) from the start of RT. The cumulative incidence of local progression (LP), locoregional progression (LRP), and distant metastasis (DM) were reported with death as a competing risk. Cox proportional hazards regression models were used to assess for correlation between patient and treatment characteristics and outcomes. RESULTS: Forty-eight patients were included for analysis. The median OS was 12.0 months [95% confidence interval (CI): 2.3–73.2 months]. The 2-, 3-, and 5-year OS were 33% (95% CI: 22–50%), 20% (95% CI: 11–36%), and 7% (95% CI: 2–20%), respectively. The 2-year PFS, LP, LRP, and DM were 21% (95% CI: 12–36%), 27% (95% CI: 17–44%), 31% (95% CI: 20–48%), and 33% (95% CI: 22–50%), respectively. On univariate analysis, biologically effective dose (BED) >59.5 Gy(10) was associated with improved OS [hazard ratio (HR): 0.40, 95% CI: 0.18–0.92, P=0.03] and PFS (HR: 0.37, 95% CI: 0.16–0.84, P=0.02) and primary tumor size (per 1 cm increase) was associated with worsened PFS (HR: 1.29, 95% CI: 1.02–1.63, P=0.04). BED >59.5 Gy(10) remained associated with PFS on multivariate analysis (HR: 0.34, 95% CI: 0.15–0.78, P=0.01). Treatment-related grade 3+ acute and late gastrointestinal AEs occurred in 13% and 17% of patients, respectively. CONCLUSIONS: RT is associated with 3- and 5-year survival in a subset of patients with unresectable EBC. Further exploration of the role of RT as part of a multi-modality curative treatment strategy is warranted.

Lymph node (LN)–positive cervical cancer is associated with a poor prognosis. We report outcomes for women with LN-positive cervical cancer treated with intensity-modulated radiation therapy (IMRT) with dose-escalated simultaneous integrated boost (SIB) to involved LNs. Between 2005 and 2017, 59 women with LN-positive, non-metastatic, cervical cancer underwent definitive chemoradiotherapy (CRT) with an image-guided LN boost to a median dose of 56.25 Gy in 25 fractions. Acute and late adverse events (AEs) were recorded per common terminology criteria for adverse events. The Kaplan-Meier method was used to estimate the overall survival (OS), progression-free survival (PFS), and locoregional control (LRC). Median age was 49 years (IQR 37–56). Women had involved LNs in the pelvis (56%) or pelvis and para-aortic (PA) LNs (44%), with a median of 3 (IQR 2–6) grossly involved LNs per patient. Median follow-up was 30 months (IQR 11–45). Estimated 3-year OS, PFS, and LRC were 67% (95% CI, 51%–84%), 60% (95% CI, 45%–76%), and 89% (95% CI, 76%–99%), respectively. PA LN involvement (HR 2.51; 95% CI, 1.05–5.99; p = 0.04) and the presence of ≥ 4 grossly involved LNs (HR 2.79; 95% CI, 1.16–6.71; p = 0.02) were associated with a higher risk of disease progression on univariate analysis. The incidence of treatment-related acute grade 3+ acute GI or GU AEs was 3%, while late GI or GU treatment-related AEs occurred in 12%. Chemoradiation with a LN-directed SIB for women with LN-positive cervical cancer is well tolerated and is associated with excellent oncologic outcomes. In this report, we evaluated the oncologic efficacy and adverse events associated with definitive chemoradiotherapy with a simultaneous integrated boost to grossly involved lymph nodes for women with lymph node–positive cervical cancer. We have identified acceptable rates of adverse events and excellent oncologic outcomes, even in a very high risk cohort of women with cervical cancer.

Purpose To understand how verification computed tomography-quality assurance (CT-QA) scans influenced clinical decision-making to replan patients with head and neck cancer and identify predictors for replanning to guide intensity-modulated proton therapy (IMPT) clinical practice. Patients and Methods We performed a quality-improvement study by prospectively collecting data on 160 consecutive patients with head and neck cancer treated using spot-scanning IMPT who underwent weekly verification CT-QA scans. Kaplan-Meier estimates were used to determine the cumulative probability of a replan by week. Predictors for replanning were determined with univariate (UVA) and multivariate (MVA) Cox model hazard ratios (HRs). Logistic regression was used to determine odds ratios (ORs). P Results Of the 160 patients, 79 (49.4%) had verification CT-QA scans, which prompted a replan. The cumulative probability of a replan by week 1 was 13.7% (95% confidence interval [CI], 8.82-18.9), week 2, 25.0% (95% CI, 18.0-31.4), week 3, 33.1% (95% CI, 25.4-40.0), week 4, 45.6% (95% CI, 37.3-52.8), and week 5 and 6, 49.4% (95% CI, 41.0-56.6). Predictors for replanning were sinonasal disease site (UVA: HR, 1.82, P = .04; MVA: HR, 3.64, P = .03), advanced stage disease (UVA: HR, 4.68, P 60 Gy equivalent (GyE; relative biologic effectiveness, 1.1) (UVA: HR, 1.99, P Conclusions Weekly verification CT-QA scans frequently influenced clinical decision-making to replan. Additional studies that evaluate the practice of monitoring IMPT-treated patients with weekly CT-QA scans and whether that improves clinical outcomes are warranted.

Purpose The relative biologic effectiveness (RBE) rises with increasing linear energy transfer toward the end of proton tracks. Presently, there is no consensus on how RBE heterogeneity should be accounted for in breast cancer proton therapy treatment planning. Our purpose was to determine the dosimetric consequences of incorporating a brachial plexus (BP) biologic dose constraint and to describe other clinical implications of biologic planning. Methods and Materials We instituted a biologic dose constraint for the BP in the context of MC1631, a randomized trial of conventional versus hypofractionated postmastectomy intensity modulated proton therapy (IMPT). IMPT plans of 13 patients treated before the implementation of the biologic dose constraint (cohort A) were compared with IMPT plans of 38 patients treated on MC1631 after its implementation (cohort B) using (1) a commercially available Eclipse treatment planning system (RBE = 1.1); (2) an in-house graphic processor unit-based Monte Carlo physical dose simulation (RBE = 1.1); and (3) an in-house Monte Carlo biologic dose (MCBD) simulation that assumes a linear relationship between RBE and dose-averaged linear energy transfer (product of RBE and physical dose = biologic dose). Results Before implementation of a BP biologic dose constraint, the Eclipse mean BP D0.01 cm3 was 107%, and the MCBD estimate was 128% (ie, 64 Gy [RBE = biologic dose] in 25 fractions for a 50-Gy [RBE = 1.1] prescription), compared with 100.0% and 116.0%, respectively, after the implementation of the constraint. Implementation of the BP biologic dose constraint did not significantly affect clinical target volume coverage. MCBD plans predicted greater internal mammary node coverage and higher heart dose than Eclipse plans. Conclusions Institution of a BP biologic dose constraint may reduce brachial plexopathy risk without compromising target coverage. MCBD plan evaluation provides valuable information to physicians that may assist in making clinical judgments regarding relative priority of target coverage versus normal tissue sparing.

Purpose To report reconstructive outcomes of patients treated with post-mastectomy intensity modulated proton therapy (IMPT) following immediate breast reconstruction (IBR). Materials and methods Consecutive women with breast cancer who underwent implant-based IBR and post-mastectomy IMPT were included. Clinical characteristics, dosimetry, and acute toxicity were collected prospectively and reconstruction complications retrospectively. Results Fifty-one women were treated between 2015 and 2017. Forty-two had bilateral reconstruction with unilateral IMPT. The non-irradiated contralateral breasts served as controls. Conventional fractionation (median 50 Gy/25 fractions) was administered in 37 (73%) and hypofractionation (median 40.5 Gy/15 fractions) in 14 (27%) patients. Median mean heart, ipsilateral lung V20Gy, and CTV-IMN V95% were 0.6 Gy, 13.9%, and 97.4%. Maximal acute dermatitis grade was 1 in 32 (63%), 2 in 17 (33%), and 3 in 2 (4%) patients. Surgical site infection (hazard ratio [HR] 13.19, 95% confidence interval [CI] 1.67–104.03, p = 0.0012), and unplanned surgical intervention (HR 9.86, 95% CI 1.24–78.67, p = 0.0068) were more common in irradiated breasts. Eight of 51 irradiated breasts and 2 of 42 non-irradiated breasts had reconstruction failure (HR 3.59, 95% CI 0.78–16.41, p = 0.084). Among irradiated breasts, hypofractionation was significantly associated with reconstruction failure (HR 4.99, 95% CI 1.24–20.05, p = 0.024), as was older patient age (HR 1.14, 95% CI 1.05–1.24, p = 0.002). Conclusions IMPT following IBR spared underlying organs and had low rates of acute toxicity. Reconstruction complications are more common in irradiated breasts, and reconstructive outcomes appear comparable with photon literature. Hypofractionation was associated with higher reconstruction failure rates. Further investigation of optimal dose-fractionation after IBR is needed.

Background Radiographic leptomeningeal disease (LMD) develops in up to 30% of patients following postoperative stereotactic radiosurgery (SRS) for brain metastases. However, the clinical relevancy of this finding and outcomes after various salvage treatments are not known. Methods Patients with brain metastases, of which 1 was resected and treated with adjunctive SRS, and who subsequently developed LMD were combined from 7 tertiary care centers. LMD pattern was categorized as nodular (nLMD) or classical (“sugarcoating,” cLMD). Results The study cohort was 147 patients. Most patients (60%) were symptomatic at LMD presentation, with cLMD more likely to be symptomatic than nLMD (71% vs. 51%, P = 0.01). Salvage therapy was whole brain radiotherapy (WBRT) alone (47%), SRS (27%), craniospinal radiotherapy (RT) (10%), and other (16%), with 58% receiving a WBRT-containing regimen. WBRT was associated with lower second LMD recurrence compared with focal RT (40% vs 68%, P = 0.02). Patients with nLMD had longer median overall survival (OS) than those with cLMD (8.2 vs 3.3 mo, P < 0.001). On multivariable analysis for OS, pattern of initial LMD (nodular vs classical) was significant, but type of salvage RT (WBRT vs focal) was not. Conclusions Nodular LMD is a distinct pattern of LMD associated with postoperative SRS that is less likely to be symptomatic and has better OS outcomes than classical “sugarcoating” LMD. Although focal RT demonstrated increased second LMD recurrence compared with WBRT, there was no associated OS detriment. Focal cranial RT for nLMD recurrence after surgery and SRS for brain metastases may be a reasonable alternative to WBRT.

Purpose Postoperative stereotactic radiosurgery (SRS) is associated with up to 30% risk of subsequent leptomeningeal disease (LMD). Radiographic patterns of LMD (classical sugarcoating [cLMD] vs. nodular [nLMD]) in this setting has been shown to be prognostic. However, the association of these findings with neurologic death (ND) is not well described. Methods and Materials The records for patients with brain metastases who underwent surgical resection and adjunctive SRS to 1 lesion (SRS to other intact lesions was allowed) and subsequently developed LMD were combined from 7 tertiary care centers. Salvage radiation therapy (RT) for LMD was categorized according to use of whole-brain versus focal cranial RT. Results The study cohort included 125 patients with known cause of death. The ND rate in these patients was 79%, and the rate in patients who underwent LMD salvage treatment (n = 107) was 76%. Univariate logistic regression demonstrated radiographic pattern of LMD (cLMD vs. nLMD, odds ratio: 2.9; P = .04) and second LMD failure after salvage treatment (odds ratio: 3.9; P = .02) as significantly associated with ND. The ND rate was 86% for cLMD versus 68% for nLMD. Whole-brain RT was used in 95% of patients with cLMD and 52% with nLMD. In the nLMD cohort (n = 58), there was no difference in ND rate based on type of salvage RT (whole-brain RT: 67% vs. focal cranial RT: 68%, P = .92). Conclusions LMD after surgery and SRS for brain metastases is a clinically significant event with high rates of ND. Classical LMD pattern (vs. nodular) and second LMD failure after salvage treatment were significantly associated with a higher risk of ND. Patients with nLMD treated with salvage focal cranial RT did not have higher ND rates compared with WBRT. Methods to decrease LMD and the subsequent high risk of ND in this setting warrant further investigation.

PURPOSE/OBJECTIVE(S) No standard treatment paradigm for previously irradiated, locally recurrent rectal cancer (LRRC) exists. We present comparative oncologic, toxicity, and cost data of previously irradiated patients with LRRC undergoing CIRT versus combined modality therapy (CMT). MATERIALS/METHODS Patients with LRRC treated between 2006 and 2019 with CIRT alone (n = 85, 70.4 Gy in 16 fractions) at institution A, or CMT (n = 86, photon external beam radiotherapy 30 Gy in 15 fractions with concurrent chemotherapy followed by resection and intraoperative radiotherapy) at institution B were retrospectively compared. Overall survival (OS), pelvic re-recurrence (PR), and distant metastases (DM) were analyzed using the Kaplan-Meier method and competing risk model to report cumulative incidence. Treatment modality was compared using the Cox proportional hazards model. Acute and late toxicities, as well as a 2-year costs were compared. RESULTS Median time to follow-up or death was 6.5 years. Median OS in the CIRT and CMT cohorts were 4.5 years and 2.6 years, respectively (HR 0.50 (0.33 - 0.76), P < 0.01). Two- and five-year OS were 83.1% (75.0 - 92.0) and 46.8% (35.2 - 62.3) for CIRT patients and 62.5% (52.5 - 74.4) and 25.7% (17.4 - 38.1) in CMT patients. The five-year cumulative incidence of PR was 53.6% (43.1 - 66.7) for CIRT patients and 36.7% (27.2 - 49.3) in CMT patients (HR 1.40 (0.87 - 2.27), P = 0.17). The five-year cumulative incidence of DM was 61.4% (51.2 - 73.5) for CIRT patients and 50.6% (40.4 - 63.2) in CMT patients (HR 1.20 (0.79 - 1.83), P = 0.39). Acute and late toxicities favored CIRT (Table 1). Costs (over a 2-year period) were higher for CMT than CIRT (median: $96,499 vs. $30,144). CONCLUSION Oncologic outcomes were similar for patients treated with CIRT or CMT, although patient morbidity and cost were lower with CIRT. OS was better with CIRT, potentially attributable to differences in baseline patient health, comorbidities; although, tumor biology cannot be excluded. Prospective comparative studies are needed.

Background: Chordomas are rare tumors that arise from notochordal remnants. Although maximal safe resection is the preferred initial management, radiotherapy is used in the adjuvant setting or primarily in nonsurgical candidates. Carbon ion radiotherapy (CIRT), as an alternative to surgery alone or conventional radiotherapy modalities, has shown promising results to date. Methods: Baseline and tumor-related characteristics from two institutional cohorts were collected for patients diagnosed with sacral chordomas. Univariable logistic regression was performed to evaluate the association between treatment type and oncologic and toxicity outcomes. Overall survival (OS) and progression-free survival were estimated using the Kaplan-Meier method and compared using the Cox proportional hazards model. The National Cancer Database (NCDB) was also queried for sacral chordoma patients and included in OS analyses. Additionally, a comparison of cost between surgery and CIRT therapy was performed. Findings: A total of 919 patients were included in the study. Comparison of the institutional cohort (en bloc resection) to CIRT showed similar oncologic and toxicity outcomes, despite larger tumors in the CIRT group. The CIRT group experienced lower rates of peripheral motor neuropathy (OR: 0.13 [95% CI 0.04-0.40], p

The majority of esophageal cancer patients are diagnosed with locoregionally confined disease, which is often amenable to curative intent therapy. Chemoradiotherapy (CRT) improves overall survival (OS) in stage II and III esophagus cancer in the neoadjuvant and definitive settings. Due to the close proximity of organs at risk (OARs), including lungs, heart, stomach, bowel, kidneys, and spinal cord, esophageal CRT can result in profound acute and late toxicities. Acute toxicities can include esophagitis, nausea, vomiting, fatigue, and cytopenias. Late complications may also occur months or years after completion of thoracic radiotherapy, including significant cardiac, pulmonary, liver, kidney, or bowel toxicities, which can be life-threatening or fatal. Photon-based radiotherapy exposes OARs to significant doses of radiation, whereas proton beam therapy (PBT) has unique physical properties, as it lacks an exit dose. This allows PBT to deliver, a more conformal dose to the target and minimize the volume of OARs exposed to radiation. This dosimetric advantage may portend an increased therapeutic ratio of CRT for esophagus cancer. The objective of this review is to discuss the evolution of photon and proton-based radiotherapy techniques, rationale, dosimetric and clinical studies comparing outcomes of photon- and proton-based techniques, ongoing prospective trials, and future directions of PBT as a means of reducing toxicity and improving oncologic outcomes for patients with esophagus cancer.

Background Patterns of recurrence and survival with different surgical and radiotherapy (RT) techniques were evaluated to guide RT target volumes for patients with temporal lobe glioma. Methods and Materials This retrospective cohort study included patients with World Health Organization grades II to IV temporal lobe glioma treated with either partial (PTL) or complete temporal lobectomy (CTL) followed by RT covering both the parenchymal and dural resection bed (whole-cavity radiotherapy [WCRT]) or the parenchymal resection bed only (partial-cavity radiotherapy [PCRT]). Patterns of recurrence, progression-free survival (PFS) and overall survival (OS) were evaluated. Results Fifty-one patients were included and 84.3% of patients had high-grade glioma (HGG). CTL and PTL were performed for 11 (21.6%) and 40 (78.4%) patients, respectively. Median RT dose was 60 Gy (range, 40-76 Gy). There were 82.4% and 17.6% of patients who received WCRT and PCRT, respectively. Median follow-up time was 18.4 months (range, 4-161 months). Forty-six patients (90.2%) experienced disease recurrence, most commonly at the parenchymal resection bed (76.5%). No patients experienced an isolated dural recurrence. The median PFS and OS for the PCRT and WCRT cohorts were 8.6 vs 10.8 months (P = .979) and 19.9 vs 18.6 months (P = .859), respectively. PCRT was associated with a lower RT dose to the brainstem, optic, and ocular structures, hippocampus, and pituitary. Conclusion We identified no isolated dural recurrence and similar PFS and OS regardless of postoperative RT volume, whereas PCRT was associated with dose reduction to critical structures. Omission of dural RT may be considered a reasonable alternative approach. Further validation with larger comparative studies is warranted.

Background Randomized controlled trials (RCTs) are the gold standard for evidence-based practice, but their development and implementation is resource intensive. We aimed to describe modern RCTs in gastrointestinal (GI) cancer and identify predictors of successful accrual and publication. Materials and Methods ClinicalTrials.gov was queried for phase III GI cancer RCTs opened between 2010 and 2019 and divided into two cohorts: past and recruiting. Past trials were analyzed for predictors of successful accrual and the subset with ≥3 years follow-up were analyzed for predictors of publication. Univariate and multivariable (MVA) logistic regression were used to identify covariates associated with complete accrual and publication status. Results A total of 533 GI RCTs were opened from 2010 to 2019, 244 of which are still recruiting. In the “past” trials cohort (235/533) MVA, Asian continent of enrollment was a predictor for successful accrual, whereas trials with prolonged enrollment (duration longer than median of 960 days) trended to failed accrual. Predictors for publication on MVA included international enrollment and accrual completion. Sponsorship was not associated with accrual or publication. Notably, 33% of past trials remain unpublished, and 60% of trials that were closed early remain unpublished. Conclusion Accrual rate and the primary continent of enrollment drive both trial completion and publication in GI oncology. Accrual must be streamlined to enhance the impact of RCTs on clinical management. A large portion of trials remain unpublished, underscoring the need to encourage dissemination of all trials to, at a minimum, inform future trial design. Implications for Practice Two-thirds of gastrointestinal (GI) oncology phase III randomized controlled trials successfully accrue; however, one third of these trials are unpublished and more than half of trials that close early are unpublished. The strongest predictors for publication are successful accrual and international collaborations. Initiatives to optimize the trial enrollment process need to be explored to maximize the potential for trials to engender progress in clinical practice. Moreover, this study identified a significant publication bias in the realm of GI oncology, and the field should promote reporting of all trials in order to better inform future trial questions and design.

Chemoradiotherapy (CRT) plays an essential role in the treatment of esophageal cancer as either curative or neoadjuvant therapy. When delivered with conventional photon-based techniques, multiple adjacent organs at risk including the heart, lungs, kidneys, liver, stomach, and bowel, receive considerable radiation dose which may contribute to acute and late adverse events (AEs). Proton beam therapy (PBT) offers a reduction in radiation exposure to these organs and potentially an improvement in the therapeutic ratio. Herein we discuss the emerging role of PBT for esophageal cancer, including rationale, treatment planning, early dosimetric and clinical comparisons of PBT with photon-based techniques, ongoing prospective trials, and potential areas of opportunity for the incorporation of PBT with the goal of improving outcomes for patients with esophageal cancer.

PurposeToidentify prognostic factors, define evolving patterns of care, and the effect of targeted therapies in a larger contemporary cohort of renal cell carcinoma (RCC) patients with new brain metastases (BM).Methods and materialsA multi-institutional retrospective institutional review board-approved database of 711 RCC patients with new BM diagnosed from January 1, 2006, to December 31, 2015, was created. Clinical parameters and treatment were correlated with median survival and time from primary diagnosis to BM. Multivariable analyses were performed.ResultsThe median survival for the prior/present cohorts was 9.6/12months, respectively (P&nbsp

Accelerated partial breast irradiation (APBI) and whole breast irradiation (WBI) are treatment options for early-stage breast cancer. The purpose of this study was to compare patient-reported-outcomes (PRO) between patients receiving multi-channel intra-cavitary brachytherapy APBI or WBI. Between 2012 and 2015, 131 patients with ductal carcinoma in situ (DCIS) or early stage invasive breast cancer were treated with adjuvant APBI (64) or WBI (67) and participated in a PRO questionnaire. The linear analog scale assessment (LASA), harvard breast cosmesis scale (HBCS), PRO-common terminology criteria for adverse events- PRO (PRO-CTCAE), and breast cancer treatment outcome scale (BCTOS) were used to assess quality of life (QoL), pain, fatigue, aesthetic and functional status, and breast cosmesis. Comparisons of PROs were performed using t-tests, Wilcoxon rank-sum, Chi square, Fisher exact test, and regression methods. Median follow-up from completion of radiotherapy and questionnaire completion was 13.3 months. There was no significant difference in QoL, pain, or fatigue severity, as assessed by the LASA, between treatment groups (p > 0.05). No factors were found to be predictive of overall QoL on regression analysis. BCTOS health-related QoL scores were similar between treatment groups (p = 0.52).The majority of APBI and WBI patients reported excellent/good breast cosmesis, 88.5% versus 93.7% (p = 0.37). Skin color change (p = 0.011) and breast elevation (p = 0.01) relative to baseline were more common in the group receiving WBI. APBI and WBI were both associated with favorable patient-reported outcomes in early follow-up. APBI resulted in a lesser degree of patient-reported skin color change and breast elevation relative to baseline.

Purpose/Objective(s) Following curative resection for pancreatic ductal adenocarcinoma (PDAC), there are high rates of local recurrence. The optimal treatment of patients with isolated local recurrence (ILR) – recurrence in the abdomen without distant metastases – is not known. This study evaluated stereotactic body radiation therapy (SBRT) as a treatment option for ILR. Materials/Methods A multi-institutional retrospective analysis was performed on patients with ILR of PDAC following oncologic surgical resection treated with SBRT. Patient demographics, tumor and prior treatment characteristics, details of recurrence, SBRT treatment design and dosimetry, and patient follow-up and toxicity data were recorded from the medical record. Progression and overall survival estimates were calculated using cumulative incidence and Kaplan-Meier models, respectively. Results Between January 2010 and December 2020, 34 patients (17 males and 17 females, median age 69 years) were treated at five institutions in the United States. At the time of initial resection, most patients had T3 tumors (71%) and involved lymph nodes (71%). 31 of 34 (91%) patients underwent a Whipple procedure and 3 (9%) had a distal pancreatectomy. The R0 resection rate was 68%. 29% and 85% received neoadjuvant or adjuvant chemotherapy, respectively; and 12% and 27% had prior neoadjuvant or adjuvant radiation courses around the time of initial surgical resection. Median time to ILR was 18.7mos. The most common location of recurrence was in the pancreatic remnant or near the superior mesenteric artery. All patients underwent 5-fraction photon (28 patients) or proton (6 patients) SBRT to a median dose of 3500cGy (range 3000-4000cGy) with a median BED of 5950cGy (α/β = 10). Median follow-up after SBRT was 3.05 years. The 1-year and 2-year cumulative incidence of cancer progression were 72% (95% CI 56-93%) and 92% (95% CI 76-100%). Distant metastasis was the most common site of first recurrence (15 of 23 recurrences, 65%). 6 patients (25%) had local failure as site of first recurrence. Prior radiation was not associated with increased risk of progression after SBRT (HR 1.31 95% CI 0.56-3.07, P = 0.54). 1-year and 2-year overall survival was 64% (95% CI 49-84%) and 40% (95% CI 25-64%), with a median survival of 1.2 years from time of SBRT. Four patients (12%) developed grade 3 toxicities within one year after completion of SBRT. There were no grade 4-5 toxicities. Conclusion For treatment of PDAC ILR after surgical resection, SBRT was well tolerated and offered high rates of local tumor control with low treatment-related toxicity.

PURPOSE/OBJECTIVE(S) Whole brain radiation therapy (WBRT) is often employed as an effective treatment to palliate symptoms, improve intracranial control, and potentially improve survival for patients with brain metastasis, although it is also known to have deleterious cognitive effects. Despite multiple trials having identified strategies to help mitigate neurocognitive decline after WBRT, we hypothesized there may be barriers to integrating these techniques into routine clinical practice. The aim of this study was to characterize national practice patterns related to neurocognitive preservation strategies utilized during WBRT. MATERIALS/METHODS We conducted an online survey of all American Society for Radiation Oncology-registered radiation oncologists (RO), excluding trainees, regarding their practice patterns and attitudes towards employing memantine, an N-methyl-D-aspartate receptor antagonist, and hippocampal avoidance (HA) whole brain radiotherapy. Both techniques have been shown to reduce cognitive decline when compared to conventional whole brain radiotherapy in patients undergoing WBRT. The Pearson χ2 tests for categorical variables or student's t-test for continuous variables were used to assess associations between provider characteristics and prescribing of either memantine or HA. All statistical tests were two-sided and a P-value < 0.05 was considered statistically significant. RESULTS A total of 4,408 radiation oncologists were invited to participate in the survey, of whom 424 (9.6%) completed the survey. Among respondents, 79.6% reported having offered memantine, 72.6% HA, and 63.1% both for any of their patients undergoing WBRT. Nearly half (47.4%) of RO offered memantine for most (76-100%) of their WBRT patients. Common reasons for not offering memantine included limitations of current evidence (36.8%) as well as concerns about adverse effects (23.0%) and medication cost (23.0%). Most RO offered HA (66.5%) to a minority (1-50%) of their WBRT patients. Common reasons for not offering HA included resource-intense treatment planning and treatment delay (43.6%), concern about obtaining insurance approval (38.5%), and having no patients who met their criteria for HA (22.2%). RO with were more likely to prescribe memantine (P < 0.001), while HA was more likely prescribed by central nervous system specialists (P < 0.001) and RO in academic settings (P = 0.03). CONCLUSION Our survey suggests that the majority of respondents offer approaches for neurocognitive preservation during WBRT for their patients. However, universal and consistent adoption of these approaches may be limited by current evidence and logistical hurdles to administration. Further efforts are needed to broaden education and reduce barriers among RO in order to improve implementation of neurocognitive-sparing techniques in patients undergoing WBRT. AUTHOR DISCLOSURE V. Jairam: None. H.S. Park: Employee; Yale School of Medicine. J.B. Yu: Consultant; Augmenix / Boston Scientific. Advisory Board; Galera pharmaceuticals. R.S. Bindra: None. J.N. Contessa: None. K.R. Jethwa: Honoraria; Radoncquestions.com, LLC.

Purpose/objective(s) Following presentation of the CALGB 80803 trial, which demonstrated notably high pathologic complete response (pCR) rates with induction FOLFOX followed by chemoradiotherapy (CRT), our institution more routinely incorporated induction chemotherapy (IC) into the management of LA-EC patients. However, improvements in progression-free (PFS) or overall survival (OS) with this regimen compared to pre-operative CRT alone have not yet been shown. We hypothesized IC-CRT would lead to an improvement in OS and PFS when compared to CRT. Materials/methods Patients with operable LA-EC were eligible for analysis if they received CRT between 2013-2019. The cohort was stratified into two groups, IC-CRT vs. CRT. The Kaplan-Meier method was used to estimate OS and PFS. The cumulative incidences of local recurrence (LR), locoregional recurrence (LRR), and distant metastasis (DM) were reported. The impact of treatment group on pathologic response and surgical outcomes were assessed by Chi-square. Results 95 patients were included for analysis (IC-CRT n = 58; CRT n = 37). Baseline characteristics included median Karnofsky Performance Status 80, median weight loss 5% (IQR 0-9%), with the majority being adenocarcinoma histology (81%), T3-T4 (60%), N+ (79%), located in the distal esophagus or gastroesophageal junction (89%). Patients receiving IC-CRT were more likely to have been treated after 2016 (64% vs 38%, P = 0.021). IC was most commonly FOLFOX (74%) for a median of 3 (IQR 1-3) cycles. CRT was delivered to a median dose of 50 Gy in 25-28 fractions. Surgery was attempted in 60% and 68% of the IC-CRT and CRT cohorts, respectively. Median follow-up was 26 months. ICRT and CRT were associated with similar 2-year OS (66% [95% CI 51-78%] vs 70% [95% CI 52-83%]) and PFS (47% [95% CI 33-59%] vs 48% [95% CI 30-63%]). In the adenocarcinoma subset (n = 77), 2-year OS was 69% (95% CI 52-81%) in the IC-CRT cohort vs 61% (95% CI 40-77%) with CRT. 2-year PFS was 46% (95% CI 31-60%) and 38% (95% CI 20-56%), respectively. IC-CRT was not associated with an OS or PFS benefit among any patient subgroup. Recurrence rates were similar between the cohorts (47%) and first recurrence was most commonly DM (61% IC-CRT vs 65% CRT). Patients receiving IC-CRT compared to CRT had numeric but not statistically significant improvement in pCR (45% vs 29%, P = 0.24) and N-stage regression (72% vs 58%, P = 0.28). There was no difference in the rate of R0 resection, hospitalization, surgical complications, or treatment-related death with use of IC-CRT. Conclusion IC-CRT was not associated with improved OS or PFS in this small and perhaps underpowered cohort study. Further investigations are needed to explore the impact of IC-CRT on quality of life, symptom burden, and to see if meaningful trends develop with time.