Course Of RT Research Articles

Discordance of patient- and physician-reported toxicities in two prospective trials of stereotactic body radiotherapy (SBRT) for localized prostate cancer.

245 Background: SBRT for localized prostate cancer (PCa) is the focus of several ongoing and reported high-impact trials, which often focus on physician-reported toxicity (P-Tox) when comparing regimens. Patient-reported quality of life (PR-QoL) may differ and provide a more sensitive comparative metric of treatment burden, especially with fewer provider interactions during SBRT than during protracted RT courses. We evaluated the concordance of prospective genitourinary (GU) and gastrointestinal (GI) P-Tox and PR-QOL in men receiving SBRT for PCa. Methods: Data from two concurrently-enrolled prospective trials of SBRT in high-risk (Phase I Safety Endpoint, NCT01896271) and low-intermediate risk (Phase II GI Toxicity Endpoint, NCT02353832) PCa were used. Matching standardized schedules of collected PR-QoL [Expanded Prostate Cancer Index Composite (EPIC)] and P-Tox (CTCAE v5.0) were analyzed over the first 18 months of follow up, where symptoms are most pronounced. We assessed concordance of Grade≥2 GU/GI physician reported toxicity with PR-QoL declines exceeding anchor based minimal clinically important difference (MCID) thresholds (-6 urinary and -5 bowel summary scores, respectively) for each patient at each time point. Patients without baseline PR-QoL data were excluded in full, while time points with missing PR-QoL or P-Tox were excluded individually without imputation. Concordance was evaluated by Cohen’s kappa statistic. Results: From 101 patients, there were 256 (64%) follow up observations through 18 months with both PR-QoL and P-Tox at the time point and baseline. Concordance of PR-QoL and P-Tox was low at all time points for both GU and GI toxicity domains (mean kappa 0.093; Table). MCID was more often reported by patients than Grade≥2 toxicity by physicians (38% vs 17% for GU and 44% vs 10% for GI). There was little overlap of PR-QoL and P-Tox reporting: Grade≥2 P-Tox reported in 17% of observations with MCID in PR-QoL, while MCID in PR-QoL reported in 54% of observations of Grade ≥2 P-Tox. Mean concordance was similarly low when analyzing sub-groups of trial, investigator, and an alternative 2xMCID threshold. Conclusions: P-Tox and PR-QoL differed dramatically in two prospective studies of SBRT despite toxicity primary endpoints. This may reflect subjective and varying intervention thresholds driving P-Tox reporting, rather than actual patient burden. These data strongly support use of PR-QoL rather than P-Tox for SBRT comparative study endpoints and guidelines in this rapidly evolving space. [Table: see text]

Changing pattern of radiation therapy for bone metastases in an Australian population-based cohort of men with prostate cancer.

To evaluate the pattern of use of single-fraction conformal radiation therapy (SF-RT) and advanced radiation therapy techniques (ART), including stereotactic body radiation therapy (SBRT), for management of bone metastases (BM) in a population-based cohort of Australian men with prostate cancer (PCa) PATIENT AND METHODS: We reviewed men with metastatic PCa who received RT for BM between 2012 and 2017 as captured in the statewide Victorian Radiotherapy Minimum Data Set (VRMDS). The primary outcomes were: proportion of RT courses using SF-RT and ART. The Cochrane-Armitage test for trend was used to evaluate the changing pattern of SF-RT and ART over time. Multivariate analyses were used to identify factors associated with the primary outcomes RESULTS: Of the 4,324 courses of palliative RT for BM, 767 (17.7%) were SF-RT, and 615 (14.2%) were ART. There was no evidence of change in SF-RT use over time (P-trend=0.13). In multivariate analyses, increasing age at RT, site of BM (rib, shoulder, pelvis, and extremities), patients' area of residence (regional and remote), and treatment in public and metropolitan centres were associated with increased likelihood of SF-RT use. There was marked increase in ART use from 0.2% in 2012 to 24% in 2017 (11% intensity modulated RT, 13% SBRT) (P-trend<0.001). In multivariate analyses, younger age at RT, site of BM (rib and pelvis), higher socioeconomic status, and treatment in private and metropolitan centres were associated with increased likelihood of ART use. SF-RT continues to be a clear minority of RT schedules employed in management of BM in PCa, and the adoption of SF-RT use should be encouraged in men with limited prognosis. There has been increasing use of ART, especially SBRT, for BM in PCa over time, and we expect this will continue to increase in the era of metastatic-directed treatment for PCa.

Toxicities and Locoregional Control After External Beam Chest Wall and/or Regional Lymph Node Re-irradiation for Recurrent Breast Cancer.

To evaluate toxicities and clinical outcomes in breast cancer (BC) patients who underwent external beam chest wall (CW) and/or regional lymph node (LN) re-irradiation (re-RT) for locoregional recurrence (LRR). We performed a retrospective review of our institutional database to identify BC patients diagnosed with an isolated ipsilateral CW or nodal recurrence after prior whole breast/CW irradiation. Fifteen patients met the study criteria. Median time between completion of RT courses was 68.3 months (range=7.8-245.4 months). Median CW re-RT dose was 45 Gy (range=42.3-50.4 Gy). The majority of patients (80%) received proton beam re-RT. Grade 2-3 dermatitis occurred in 87% patients. Grade 2-3 pain was reported by 33% of patients. At a median follow-up of 14 months (range=1.0-90.5 months), the rate of isolated LRR was 13%. Re-RT of the CW and/or regional LNs is feasible with acceptable rates of toxicity and low rates of isolated LRR.

Dosimetric Modeling of Lymphopenia in Patients With Metastatic Cancer Receiving Palliative Radiation and PD-1 Immune Checkpoint Inhibitors

PurposeRadiation therapy (RT)–associated lymphopenia may adversely affect treatment outcomes, particularly in the era of immunotherapy. We sought to determine dosimetric factors correlated with lymphopenia after palliative RT in a cohort of patients with advanced cancer treated with anti-PD-1 immune checkpoint inhibitors. Methods and MaterialsWe included patients with metastatic lung cancer, melanoma, or renal cell carcinoma who were treated with either pembrolizumab or nivolumab and received palliative RT to an extracranial site. Baseline and nadir absolute lymphocyte counts (ALCs) within 6 weeks of RT were recorded. Dosimetric factors were extracted from the corresponding dose-volume histograms and also used to model the dose to circulating lymphocytes via a whole-body blood flow model that simulates the spatiotemporal distribution of blood particles in major organs during RT. ResultsWe analyzed 55 patients who underwent 80 total courses of palliative RT; most (94%) were treated with 3-dimensional conformal RT. Doses to the whole body, bone, and large blood vessels (LBVs) were negatively correlated with the ALC nadir, with the strongest correlations seen at V15 (rs, –0.38, –0.43, and –0.37, and P = .0004, .0001, and .0008, respectively). Doses to other organs were not significantly correlated with the ALC nadir. The modeled dose to circulating lymphocytes was also negatively correlated with the ALC nadir and percent ALC change (for D2%, rs, –0.31 and –0.44, and P = .005 and .0001, respectively). Grade ≥3 lymphopenia was associated with LBV V15 (odds ratio [OR], 1.16; 95% CI, 1.07-1.26; P < .001), bone V15 (OR, 1.04; 95% CI, 1.01-1.08; P = .03), body V15 (OR, 1.003; 95% CI, 1.001-1.006; P = .008), and modeled lymphocyte dose (OR, 1.45; 95% CI, 1.16-1.82; P < .001). ConclusionsThe RT dose to the whole body, bone, and LBVs and the modeled dose to circulating lymphocytes were correlated with lymphopenia in patients treated with palliative RT and anti-PD-1 immune checkpoint inhibitors. These findings may inform future radiation planning in this setting.

Finding safe dose-volume constraints for re-irradiation with SBRT of patients with prostate cancer relapse: The IEO experience

The primary aim of this study is to provide preliminary indications for safe constraints of rectum and bladder in patients re-irradiated with stereotactic body RT (SBRT). Data from patients treated for prostate cancer (PCa) and intraprostatic relapse, from 1998 to 2016, were retrospectively collected. First RT course was delivered with 3D conformal RT techniques, SBRT or volumetric modulated arc therapy (VMAT). All patients underwent re-irradiation with SBRT with heavy hypofractionated schedules. Cumulative dose-volume values to organs at risk (OARs) were computed and possible correlation with developed toxicities was investigated. Twenty-six patients were included. Median age at re-irradiation was 75years, mean interval between the two RT courses was 5.6years and the median follow-up was 47.7months (13.4-114.3months). After re-irradiation, acute and late G≥2 GU toxicity events were reported in 3 (12%) and 10 (38%) patients, respectively, while late G≥2 GI events were reported in 4 (15%) patients. No acute G≥2 GI side effects were registered. Patients receiving an equivalent uniform dose of the two RT treatments<131Gy appeared to be at higher risk of progression (4-yr b-PFS: 19% vs 33%, p=0.145). Cumulative re-irradiation constraints that appear to be safe are D30% < 57.9Gy for bladder and D30% < 66.0Gy, D60% < 38.0Gy and V122.1 Gy<5% for rectum. Preliminary re-irradiation constraints for bladder and rectum have been reported. Our preliminary investigation may serve to clear some grey areas of PCa re-irradiation.

NCOG-01. RADIATION THERAPY MANAGEMENT FOR METASTATIC DISEASE TO THE BRAIN IN NSCLC PATIENTS – SURVIVAL OUTCOMES OF THE BRITISH COLUMBIA POPULATION 1996-2016

Abstract BACKGROUND Radiation therapy (RT) for brain metastases in patients with non-small cell lung cancer (NSCLC) has undergone considerable evolution but remains controversial. METHODS Records for 2212 patients with NSCLC who received RT to the brain at one of six locations between 1996-2016 were retrospectively analyzed. Data were obtained from the institutional cancer registry following ethics approval. Overall survival (OS) was calculated from diagnosis of lung cancer to death, and Kaplan-Meier curves were compared by Log-rank and Cox regression. RESULTS Median OS was 11.8 months (95%CI 11-12.6 months). Median age was 65, and 1254 patients (57%) were female. ECOG performance status at diagnosis was 0 (12%), 1 (31%), 2 (17%), 3 (14%), 4 (2%), and unknown (24%). Younger age (HR=0.99, 95%CI 0.98-0.99), female sex (HR=0.80, 95%CI 0.74-0.88), and better ECOG performance status (p&amp;lt; 0.0001) were associated with superior OS. There was better OS in 932 patients (42%) that received chemotherapy (HR=0.63, 95%CI 0.58-0.69) and 603 (27%) that underwent surgery (HR=0.55, 95%CI 0.50-0.61). 2004 patients (91%) received 1 RT course, while 208 (9%) received multiple courses in various combinations of whole brain RT (WBRT) and stereotactic radiosurgery (SRS). SRS (HR=0.70, 95%CI 0.57-0.86) and multiple RT courses (HR=0.55, 95%CI 0.46-0.65) were associated with better OS. Median time from primary diagnosis to brain RT was 2.5 months, and from end of first brain RT to death was 3.5 months. A longer diagnosis to brain RT interval was associated with better OS (HR=0.95, 95%CI 0.95-96). CONCLUSIONS NSCLC patients with brain metastases continue to face poor prognosis, particularly when lung cancer diagnosis to first brain RT interval is short. Our analysis revealed younger age, female sex, and better ECOG performance status as predictors of superior survival. SRS and multiple RT courses also revealed superior survival, likely the result of patient selection and hence interpreted with caution.

РОЛЬ ИНТЕНСИФИКАЦИИ НЕОАДЪЮВАНТНОГО ЛЕЧЕНИЯ БОЛЬНЫХ МЕСТНОРАСПРОСТРАНЕННЫМ РАКОМ ПРЯМОЙ КИШКИ

Purpose: To improve the effectiveness of treatment of patients with locally advanced rectal cancer (LARC) stage T3(MRF+)-4N0-2M0 by developing a new strategy of therapy. &#x0D; Material and methods: The study included 414 patients with LARC. Control group I included 89 patients who underwent neoadjuvant CRT 52–56 Gy with capecitabine. Control group II included 160 patients, underwent neoadjuvant CRT 52–56 Gy with capecitabine and oxaliplatin once a week, during the course of RT. Study group III - 165 patients. This group combined neoadjuvant CRT 52–56 Gy with capecitabine and additional consecutive courses of chemotherapy (CT) in the CapOx mode. This group, depending on the variant of chemotherapy, was divided into 2 subgroups: subgroup IIIa included 106 patients with consolidating CT (after CRT); subgroup IIIb included 59 patients who underwent "sandwich" treatment. Therapy consists of conducting 1 or 2 courses of induction CT (up to CRT) in the CapOx mode and 1 or 2 courses of consolidating CT in the CapOx mode with an interval of 7 days. In the interval between the courses of drug therapy, prolonged CRT was performed. According to the results of the control examination, further treatment tactics were determined. &#x0D; Results: IComplete therapeutic pathomorphosis in the tumor was significantly more frequently registered in patients in the study group III (17.5 %; p=0.021) compared to the control groups: in I – 8.0 % and II – 8.3 %. In total, relapses in the study were registered in 34 (8.3 %) of 410 patients. A comparative analysis of patients in the control groups (I and II) of treatment did not determine significant differences in the development of relapses (11.4 % vs. 10.8 %, respectively; p=0.884). When analyzing the subgroups (IIIa and IIIb) of the study group, there were also no significant differences in the development of relapses (4.8 % vs. 3.4 %; p=0.676). In the present study, long-term metastases at various times after treatment were diagnosed in 100 (24.4 %) of 410 patients. All metastases occurred at a median follow-up of 20.9 months (4 to 46 months). Metastases were significantly less frequent in patients in group III (18.3 %) compared to group I (31.8 %; p=0.015) and II (26.6 %; p=0.037). There were no significant differences between patients in group I and II (p=0.382). The analysis of the treatment subgroups of the study group (IIIa and IIIb) did not determine significant differences in the development of metastases (19.1 % vs. 17.0 %; p=0.456). The overall five-year survival rate in patients in group III was 90.5 %, in group I – 71.8% and in group II – 78.3%. Five-year relapse-free survival in patients in the study groups was: III – 71.5%, I – 56.9% and II – 65.6%, respectively. &#x0D; Conclusion: The shift in the focus on strengthening the neoadjuvant effect on the tumor and the improvement of approaches to drug therapy regimens allowed to significantly increase the relapse-free survival in this category of patients.

The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonization Group Recommendations for Сontouring of OARs

QUANTEC report summarized the data of the dose constrains for critical structures in radiotherapy. The authors of this report determined that one of the obstacles to obtaining meaningful data on tolerant doses was inconsistency in the nomenclature of names. And inconsistencies in the guidelines for contouring the organs at risk increase the variability in contouring. Eliminating these inconsistencies increases the speed and safety of the workflow within each individual healthcare facility and improves the accuracy and reliability of the data underlying the dose limits that are developed. The standardization of terminology facilitates the integration of dosimetry data, the creation of various templates and scripts to automate the creation of a prescription for the RT course for similar cases, and the automation of reports. It helps to train the systems supporting artificial intelligence. AAPM report TG-263 resolved the nomenclature problem, however, different anatomical boundaries of different organs were still hidden under the same names in various large research centers. In 2020 The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonization Group published an article. It summarized the many years of work by the scientific radiotherapy community to standardize the approach to delineating the OARs. This article provides an overview of the article key points and provides links to outline guides.&#x0D; A special attention it was paid to clarifying the anatomical boundaries of such OARs: heart, femoral heads, skin, individual structures of the gastrointestinal tract and substructures of the eye.

CA209-9KY: Phase II Study of IMRT Re-Irradiation and Concurrent/Adjuvant Nivolumab (Nivo) in Patients With Loco Regionally Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma (HNSCC) ― Toxicity and Quality of Life (QoL) Results

CA209-9KY: Phase II Study of IMRT Re-Irradiation and Concurrent/Adjuvant Nivolumab (Nivo) in Patients With Loco Regionally Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma (HNSCC) ― Toxicity and Quality of Life (QoL) Results

Concurrent Radiation Therapy With the Antibody-Drug Conjugates Brentuximab Vedotin and Polatuzumab Vedotin

Brentuximab vedotin (BV) and polatuzumab vedotin (PV) are antibody-drug conjugates targeting CD30 and CD79B, respectively, approved for the treatment of select T- and B-cell lymphomas. Safety data to inform the use of concurrent radiation therapy (CRT) with BV or PV is lacking.We retrospectively reviewed 31 patients (pts) who received CRT with BV or PV from 5/2018 to 1/2021. We defined CRT as infusion within 3 weeks prior to or concurrent with RT. Timing of toxicity (CTCAE v5.0) was classified as pre-RT (within 1 month prior to RT), acute (start to 1 month post-RT), and subacute (2-3 months following RT), censored at subsequent systemic therapy. Statistics were performed using Mann-Whitney U and Chi-squared tests.Of 31 pts, 20 (65%) received BV and 11 (35%) received PV. Median age at CRT was 55 (range 27-88), and 14 pts were female (45%). 26 pts (84%) had stage III-IV disease at the time of CRT. The most common diagnoses were mycosis fungoides (12 pts, 39%; 7 with large cell transformation) and diffuse large B cell lymphoma (10 pts, 32%). Pts received a median of 4 lines of prior systemic therapy (range 0-8). 22 pts received prior RT courses (median 1, range 1-6). Fourteen pts received combination regimens with BV or PV: bendamustine and rituximab (R) (5, 16%); cyclophosphamide (C) (± R) (3, 10%); R alone (5, 16%); and C with doxorubicin (1, 3%). Eleven pts (35%) were treated with electrons targeting skin, with a median dose of 12 Gy (range 4-32). Twenty pts (65%) were treated with photons to 32 sites, with a median dose of 25 Gy (range 9-44); treatment sites included the spine (14 pts, 45%), abdomen/pelvis (9 pts, 29%), and brain (3 pts, 10%). Median percent bone marrow (BM) treated was 6.6 (range 0-18.3). The rate of grade 2 or higher (G2+) hematologic toxicity (HT) was 45% (14/31) pre-CRT vs. 79% (23/29) in the acute setting (P = 0.044) and 71% (10/14) in the subacute setting (P = 0.29). There was no significant change in acute or subacute pain, fatigue, diarrhea, neuropathy, or hepatotoxicity following CRT. Acute G2+ HT was associated with pre-RT G2+ HT (P = 0.019) and more lines of prior systemic therapy (P = 0.011). Percentage of BM irradiated was not significantly associated with acute G2+ HT (P = 0.09). Age, concurrent chemotherapy with BV or PV, prior RT courses, RT dose, and RT modality were not associated with G2+ HT. Six pts (19%) were bridged to stem cell transplant at a median of 26 days (IQR 16-52). 12 patients (39%) received subsequent systemic therapy for progression at a median of 81 days (IQR 25-87). Median time to progression or last follow-up was 72 days (IQR 20-113). At last follow-up, 18 pts (58%) were deceased; median overall survival from CRT was 177 days (95% CI 92-263).CRT with BV or PV was overall well tolerated. We observed HT, particularly in patients with cytopenias prior to RT. Care should be taken during RT planning to reduce this risk if possible.

Low Rate of Local Salvage Therapy Following Radiation Therapy for Non-Spine Bone Metastases ― An Indication for Appropriate Patient Selection

<h3>Purpose/Objective(s)</h3> Local therapy for patients with non-spine bone metastases is evolving, with recent data suggesting that stereotactic body radiotherapy (SBRT) may improve pain response in the palliative setting. However, the rate of local salvage therapy (LST) after SBRT compared to conventional RT is unknown. We therefore characterized rates and risk factors for LST in patients with non-spine bone metastases. <h3>Materials/Methods</h3> We reviewed records of all courses of RT for non-spine bone metastases at our institution from 1/1/2016 to 12/31/2018. LST was defined as the first occurrence of either RT or surgery for progression to a bone metastasis following initial RT. Functions of the cumulative incidence of re-treatment were generated for each RT technique. We identified associations with various predictors using the Fine and Gray method for competing risk regression. <h3>Results</h3> Of the 1,754 patients included, 2,648 bone metastases were treated with RT and analyzed with a median follow up of 15 months (IQR = 6.4 – 25.0 months). 51% of episodes were multi-fraction EBRT, 10% were single fraction EBRT, and 39% were SBRT. Of the treated metastases, 120 (4.5%) episodes required LST (median time to LST = 6.2 months, range = 0.3-35.6 months), with a cumulative incidence at 6 and 12 months of 2.4% and 3.9%, respectively. Cumulative incidence of re-treatment at 6 months was 2.6% for SBRT, 3.5% for single-fraction conventional, and 2.1% for multi-fraction conventional regimens (<i>P</i> = 0.76). On multivariable analysis, younger age, higher Karnofsky performance status (KPS), and location of the metastasis in the pelvis had higher hazard of re-treatment (Table 1). There was no significant difference in hazard of LST among RT techniques (<i>P</i> = 0.44), nor was there a significant interaction between RT technique and radioresistant histology (<i>P</i> = 0.33). <h3>Conclusion</h3> In our large institutional cohort, the rate of LST was low, with no difference between RT techniques. Our results suggest that judicious selection of patients at high risk for eventual treatment failure (i.e., those with longer expected survival) for SBRT may reduce the rate of retreatment rate in the population. When patients are appropriately selected for single fraction conventional RT, such as those who are older or have poor KPS, rates of LST remain low. Further studies to validate our findings are warranted to help clinicians to select the appropriate treatment technique for patients with bone metastases.

Disease Outcomes Following Low-Dose Radiotherapy vs. Moderate-Dose Radiotherapy for Orbital Low Grade Non-Hodgkin Lymphoma

Orbital low grade non-Hodgkin Lymphomas (LGNHLs) are a common tumor of the ocular adnexa. Courses of low-dose radiotherapy (LDRT), previously defined as 2 Gray (Gy) x 2 fractions, have resulted in excellent short-term outcomes for orbital LGNHLs. Recent data, however, suggests that higher doses are associated with improvements in response rates and progression free survival. RT is a proven treatment modality for this entity, but no prior data exists comparing outcomes following LDRT to moderate-dose RT (MDRT, RT dose > 4 Gy). Herein, we compare outcomes including overall response rates (ORR), local control (LC) and overall survival (OS) for patients treated with LDRT vs MDRT.We reviewed 38 consecutive courses of RT for 36 patients treated for orbital LGNHL at a single institution. Bilateral disease was present in 15 patients. Nine patients had advanced stage disease or secondary orbital lymphoma following systemic dissemination. Indolent histologies included marginal zone lymphoma (20 patients), follicular lymphoma (11 patients), and mantle cell lymphoma (MCL, 5 patients). ORR were recorded according to Deauville or RECIST criteria with a response characterized as a complete response (CR) or partial response. Time to orbital recurrence (TTOR) and OS were estimated with the Kaplan-Meier (KM) method from start of RT to event or last follow-up. Univariate and multivariate Cox regression analysis was performed for characteristics associated with the studied outcomes. RT toxicity was graded per CTCAEv5.Median follow-up time for all patients was 29 months (m) (range, 4-129m) and median MDRT dose used was 24 Gy (range 21-36 Gy) in 1.5-2 Gy fractions. LDRT was delivered for 14 courses and MDRT for 24 courses. Advanced stage (odds ratio (OR) 7, P = 0.021) and year of RT ≥2016 (OR 24, P = 0.008) were associated with increased use of LDRT as compared to MDRT. Acute grade 1 (G1) and G2 RT toxicities occurred following 22 (58%) and 5 (13%) courses, respectively. No ≥G3 acute toxicities occurred. Late toxicities included 6 patients with G1 dry eye (4 MDRT, 2 LDRT), 3 patients with G2 dry eye (3 MDRT) and one patient with a G1 cataract (1 MDRT). ORR were 100% (CR 50%) and 87.5% (CR 58.3%) following LDRT and MDRT, respectively. No evaluated characteristics, including the use of LDRT, were significantly associated with inferior ORR, TTOR or OS. LC at 2 years was 100% and 95% for the LDRT and MDRT groups, respectively.RT for orbital LGNHL is associated with excellent outcomes in terms of response rates and local control. Due to the exquisite radiosensitivity of orbital LGNHL, LDRT produces similar response rates and TTOR as compared to more protracted RT courses. Present data suggests that LDRT should be considered for patients with orbital LGNHL; however, further multi-center studies with larger patient numbers are warranted to show significant associations.

Radiation for Anorectal Cancers in Patients With a History of Prostate Radiation Therapy

RT for rectal and anal cancer after prostate cancer RT is usually avoided due to fear of complications, and data on this topic is scarce. Our aim was to evaluate outcomes and toxicity associated with RT in this group of patients.We conducted a single institution retrospective study of patients treated with RT for rectal or anal cancer after prior prostate RT from 1/1/1995 - 8/1/2019. Acute and long-term toxicities were collected. Treatment plans were extracted to assess doses to organs at risk and target coverage. Wilcoxon rank sum test was used for correlation between dosimetry and toxicities. Estimated cumulative incidence was used for local progression.We identified 29 patients who received RT after prostate cancer RT, 19 with rectal cancer and 10 with anal cancer. None of those patients had metastatic disease. Prior prostate RT was delivered using low dose rate brachytherapy (LDR) in 15/29 patients with a median dose of 145 Gy (144-160), external beam RT (EBRT) in 10 patients with 79.2Gy/44 or 81Gy/45 fractions (fr), and EBRT + LDR in 4 patients with 50.4/28 + 80-110 Gy I-125 or Pd-103 LDR. RT for rectal cancer was delivered most commonly with 50.4Gy/28 fr or 1.5 Gy twice daily fractionation to 30-45 Gy (53% of patients). The most commonly used RT dose for anal cancer was 50Gy/25 fr. Brachytherapy was used in 6 (21%) patients: as a boost after EBRT in 2 patients with anal cancer and alone in 4 rectal cancer patients. Median interval between prostate and anorectal RT was 134 months (6-303). 68% and 80% of rectal and anal cancer patients got concurrent chemotherapy. Table 1 summarizes toxicities associated with anorectal re-RT. Two patients developed fistulas, one was urinary cutaneous after prostate LDR and 45Gy/25fr for rectal cancer, and the other recto vesicular after prostate LDR and 50Gy/25fr for anal cancer; both repaired by extensive surgery. Both patients had more than 10 years between the two RT courses. In 21 patients with available dosimetry, coverage was adequate with a GTV V100% of 98% for rectal cancer patients and 96% for anal cancer patients. There was no significant correlation between toxicities and dosimetric values probably due to the small sample size. The estimated 5-year local progression incidence for all patients was 22%: 11% for rectal cancer, and 4% for anal cancer patients.RT of anorectal cancer after prior prostate cancer RT is feasible but poses a risk of fistulae. Further studies, possibly using proton therapy and/or rectal hydrogel spacers, are needed to further establish the feasibility of RT in this context, decrease toxicity, and improve outcomes.

Impact of Fraction Size and Primary Tumor on Outcomes After Palliative Radiation for Osseous Metastases

To review palliative RT practices, outcomes, and compare the percentage of remaining life spent receiving RT (PRLSRT) for patients treated with RT for osseous metastases.A retrospective analysis was conducted using the National Cancer Database (2010-2016). Patients with bone mets who underwent palliative bone RT were included. Common palliative RT schemes (Gy/Fx) were evaluated to determine treatment patterns and outcomes. Median PRLSRT, incomplete RT courses, deaths on RT as well as 30-day and 90-day mortality rates were calculated. A logistic regression was performed to identify factors affecting completion rates.52,971 patients were included: 45.0% non-small cell lung (NSCLC), 15.1% breast, 10.8% prostate, 10.9% GI, 9.7% genitourinary, 4.9% small-cell lung (SCLC), and 3.3% other. Overall median survival after palliative RT was 5.74 months. Patients receiving lower dose per fraction (2Gy/Fx) were more likely to be younger and healthier, yet experienced worse palliative outcomes with higher median PRLSRT, rates of incompletion, and deaths on treatment (Table 1). Breast and prostate were most likely to complete RT (89.1% and 89.6%), while GI NOS and SCLC were least likely (77.6% and 78.6%) (P < 0.001). Upper GI patients were most likely to die on treatment (1.3%), while prostate patients were the least (0.2%) (P < 0.001). PRLSRT ≥50% was observed more frequently in GI NOS (16.6%), upper GI (10.4), NSCLC (10.3%), and skin (9.8%) compared to prostate (2.4%) and breast (2.7%) (P < 0.001). Logistic regression indicated age, race, insurance status, Charlson-Deyo score, primary site, metastatic involvement, bone RT site, and Gy/Fx were significant factors affecting completion rates of RT. Median PRLSRTs were: 14.89% GI NOS, 9.90% upper GI, 9.49% NSCLC, 7.89% skin, 7.18% SCLC, 6.12% lower GI, 5.64% GYN, 5.42% GU, 5.24% HNC, 2.05% prostate, and 2.02% endocrine, and 1.84% breast (P < 0.001). Those receiving 3Gy/Fx and 2Gy/Fx were less likely to complete RT when compared to 4Gy/Fx, with odds ratios of 1.209 and 15.023 respectively (P < 0.001). Patients with SCLC were least likely to complete RT, with a 1.694 odds ratio compared to breast (P < 0.001).For palliative RT for osseous metastases, dose per fraction and primary cancer impact the palliative outcomes of PRSLRT, the likelihood of completing RT, and death during treatment and should be considered to minimize the burden of care and maximize benefits of treatment.

Efficacy and Toxicity of Alternative Radiation Treatment Schemes for Patients With Hematologic Malignancies: A Collaborative ILROG COVID Era Report

Purpose/Objective(s)The COVID19 pandemic required radiation oncologists (ROs) to consider shorter treatment courses to minimize patient and staff exposure and conserve healthcare resources. Hematologic ROs adopted hypofractionated radiation therapy (hRT) regimens according to guidelines published by the International Lymphoma Radiation Oncology Group (ILROG). We report for the first time the preliminary efficacy and toxicity of these novel hypofractionated regimens in the treatment of hematologic malignancies.Materials/MethodsWe conducted a multicenter, multinational retrospective study under the direction of the ILROG. All patients receiving hRT according to ILROG guidelines from 1/1/2020 to 8/31/2020 were included. Patient and treatment details were abstracted from separate institutional databases. Toxicity was graded using CTCAE v5.0.ResultsNinety-three patients from 4 institutions treated with 114 RT courses were included. Patient and treatment details are displayed in Table 1. Median follow up for the cohort was 179 days, and 77 patients (82%) were alive at last follow up. Maximal toxicity experienced by patients included Grade 1 (n = 16), Grade 2 (n = 1) and Grade 3 (n = 1) toxicities. Of 80 sites with response assessment within the RT field, 69% of patients achieved a complete response (n = 55), 20% partial response (n = 16), 9% stable disease (n = 7), and 2% progressive disease (n = 2). No COVID19 infections during or after RT have been documented in this patient cohort.ConclusionHRT according to ILROG guidelines resulted in low rates of acute toxicity and reasonable short-term treatment efficacy. Longer follow up and comparison with control groups is needed to draw more definitive conclusions and will be presented at the Annual Meeting.

Salvage Radiotherapy for Relapsed/Refractory Non‐Hodgkin Lymphomas Following CD19 Chimeric Antigen Receptor T-Cell (CART) Therapy

<h3>Purpose/Objective(s)</h3> CD19-directed CART therapy has emerged as a promising treatment for relapsed/refractory non-Hodgkin lymphoma. However, sustained efficacy is limited with durable complete response rates of 40% (Schuster & Locke, 2019). Salvage radiotherapy (SRT) is potentially an important strategy post‐CART, but current data is limited to one series of 14 patients. <h3>Materials/Methods</h3> We retrospectively analyzed 21 patients who received SRT after commercial CART therapy between 8/2018 and 6/2020. Patients who relapsed after CART were divided into two groups: locoregional disease (LD, all relapsed disease encompassable within an RT field) and advanced disease (AD). SRT was defined as comprehensive (treated all sites of active disease) or focal. Post-SRT in-field objective response rates (ORR) were recorded according to Deauville or RECIST criteria with a response characterized as a complete response or partial response. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Acute RT toxicity was graded by CTCAEv5. <h3>Results</h3> Median time from CART infusion to SRT was 4.0 months (m) (range, 0.6-11.6m). Within the LD group, 8/9 patients were treated with comprehensive SRT (median SRT dose 37.5 Gy, range 8-45 Gy, and number fractions 15, range 2-25 fractions). The in-field ORR was 8/9 (89%). For the AD group, 12/12 patients were treated with focal SRT (median SRT dose 20.8 Gy, range 8-30 Gy, and number fractions 5, range 1-12 fractions). 11/12 AD patients were treated with hypofractionated SRT (≥2.5Gy fractions). Three patients died prior to subsequent imaging with an ORR of 8/9 (89%) for the remaining evaluable patients. Distant progression occurred in 17/18 patients post-SRT (Table). Three-month PFS was 24% for the entire cohort, and 33% and 17% for the LD and AD groups, respectively (<i>P</i> = 0.258). Median OS was 7.4m for the entire cohort, and 21.1m and 2.4m for the LD and AD groups, respectively (<i>P</i> < 0.001). Grade 1 (G1) and G2 acute SRT toxicities occurred in 10 and 4 patients, respectively. No G3 or higher toxicities occurred. <h3>Conclusion</h3> SRT post-CART therapy appears safe (no ≥G3 RT toxicities) in our series. SRT led to an ORR of 89% with only 1 observed local relapse. Patients with LD relapse post-CART had significantly improved survival compared with AD relapse. Unfortunately, prognosis remains poor as 17/18 patients with evaluable imaging progressed outside of the RT field. Thus, prolonged RT courses may not be warranted given the practical inevitability of out of field disease progression. Multi-institutional review of SRT following CART is warranted to further elucidate the impact of RT dose and fractionation on disease outcomes.

18F-DOPA-PET-Guided Re-Irradiation for Recurrent High-Grade Glioma: Initial Results of a Phase II Trial

In-field high-grade glioma (HGG) recurrence is a common challenge with limited treatment options, including re-irradiation (re-RT). Delineating re-RT target volumes is especially challenging in the setting of the VEGF-inhibitor bevacizumab, which can produce an MRI pseudo response. The radiotracer 18F-DOPA crosses the blood brain barrier and demonstrates high uptake in tumor but low uptake in normal tissue. We hypothesized that utilizing 18F-DOPA-PET with MRI for target delineation of recurrent HGG would improve progression free survival at 3 months (PFS3) compared to historical controls treated with systemic therapy only.Adults with recurrent or progressive HGG previously treated with radiation were eligible for this single-arm, phase II prospective trial. A sample size of 20 was calculated to detect a 20% improvement from the historical control PFS3 of 20%, with a power of 85.9% (alpha 0.186). Re-RT dose was 35 Gy in 10 fractions. The target volume was MRI T1 contrast-enhancement defined tumor plus 18F-DOPA-PET defined tumor (tumor/normal ratio > 1.5). Concurrent treatment with bevacizumab was encouraged but not required. Patients were followed at 1 and 3 months (primary endpoint), then every 2 months until 2 years or progression, defined by RANO criteria.Twenty patients completed treatment per protocol. Fifteen (75%) were male. Median age was 53 (range 38-69). Diagnosis was most commonly glioblastoma, IDH-wildtype (60%) or glioblastoma, IDH-mutant (20%). Prior to re-RT, 19 (95%) received previous salvage treatments including surgery (35%) and systemic therapy (90%). Bevacizumab was used prior to, during, and immediately following re-RT in 12 (60%), 14 (70%), and 16 (80%) patients, respectively. Median interval between RT courses was 21.5 months (range 5-167), with an interval > 12 months in 85%. Median MRI-defined, PET-defined, and combined tumor volumes were 17 cc (range 0-198), 14 cc (0.2-209), and 23.2 cc (4-258), respectively. MRI-defined volumes were expanded by a median 43% (0-436%) by utilizing 18F-DOPA-PET. PFS3 was 85% (95% CI: 63.2-95.8%), meeting the primary endpoint of PFS3≥40%. At data lock in January 2021 with 9.7 months median follow-up, 17 (85%) had progressed and 13 (65%) had died. Median OS from re-RT was 8.5 months, with 1- and 2-year OS estimates of 31% and 15%, respectively. Median OS from initial diagnosis was 3.7 years. Failure following re-RT was within both the MRI and PET tumor volumes in 75%, MRI only in 13%, PET only in 0%, and neither in 13%. Four (20%) patients experienced grade 3 toxicity, including CNS necrosis (n = 2, both asymptomatic with bevacizumab initiation for radiographic findings), seizures (n = 1), fatigue (n = 1), and nausea (n = 1). No grade 4-5 toxicities were observed.The 18F-DOPA-PET guided re-irradiation for progressive high-grade glioma appears safe and promising for further investigation.

Simulation Free Radiotherapy: An Emerging Form of Simulation and Treatment Planning to Simplify Palliative Radiotherapy

<h3>Purpose/Objective(s)</h3> Simulation free RT (SF-RT) is an emerging technique in which a patient's (pts) diagnostic imaging is used for simulation (sim) and treatment planning. SF-RT may increase the speed of treatment planning while reducing pt visits. In palliative care, minimizing time in the radiation oncology (RO) department and expediting treatment is critical. We evaluated clinical data for pts treated with palliative SF-RT compared to pts treated with palliative CT sim RT (CT-RT) in a retrospective matched cohort analysis. <h3>Materials/Methods</h3> From 1/2020 to 11/2020, 30 sessions of palliative SF-RT were performed at a single institution. A session was defined as a single course of palliative RT. Pts received both single and multi-fraction regimens. Time points collected included time of order approval, plan approval, and first treatment. A matched cohort of pts treated with palliative CT-RT was acquired via Reweight Mahalanobis Distance Matching matched on age, total dose, and treatment site. Descriptive statistics were calculated on all variables and statistical significance was evaluated using the Chi-square method for categorical variables and the t-test method for continuous variables. <h3>Results</h3> 30 sessions of palliative SF-RT were matched with 30 sessions of palliative CT-RT, with the median distance matching being 0.073 (0.018-0.147). Median age of pts treated with SF-RT was 61 (56-73) and median age of pts treated with CT-RT was 62 (55-72). The majority of pts in both groups were treated on an outpatient basis. The most common site treated in both groups was spine. 70% of SF-RT sessions were single fraction, and 57% of CT-RT sessions were single fraction. Mean time from order approved to plan approved was 1.8 days (d) (+/- 1.8 d) for SF-RT sessions and 3.0 d (+/- 3.4 d) for CT-RT sessions. Mean time from plan approved to first treatment was 2.3 d (+/- 2.8 d) for SF-RT sessions and 2.0 d (+/- 2 d) for CT-RT sessions. Mean time from order approved to first treatment was 4.1 d (+/- 3.3 d) for SF-RT and 5.0 d (+/- 3.8 d) for CT-RT. There were no statistically significant differences between variables. <h3>Conclusion</h3> SF-RT led to an average of .9 d faster time from order approval to first treatment while requiring one less patient visit to the RO department when compared to CT-RT. These data demonstrate the potential for SF-RT to increase the efficiency of palliative RT while reducing pt visits to the RO department.

Interaction Between Neutrophil-to-Lymphocyte Ratio, Radiotherapy Fractionation/Technique, and Risk of Development of Distant Metastasis in Locally Advanced Rectal Cancer Patients

There is a paucity of data studying the significance of neutrophil-to-lymphocyte ratio (NLR) in peripheral blood of patients with locally advanced rectal cancer (LARC) planning to undergo preoperative RT. We aimed to investigate the prognostic impact of NLR in patients with LARC and whether there are modifiable factors in RT which influencing the level of NLR.We studied 1366 patients treated with neoadjuvant RT with concurrent or sequential chemotherapy for LARC from 2006 to 2019. Most (97.8%) were treated with long-course RT (50-50.4 Gy in 25-28 fractions) with 3DCRT (n = 851) or helical tomotherapy (n = 504). Short-course RT (25 Gy in 5 fractions, followed by 6-week XELOX) was used in 30 cases (NCT03676517). The absolute neutrophil and lymphocyte counts were obtained from the sample collected at the time of initial diagnosis, before and during the course of preoperative RT and before surgery. The primary endpoint was distant metastasis-free survival (DMFS).With the median follow-up time of 61.3 months (4.1-173.7 months), the 5-year DMFS was 80.1%. 5-year DMFS was significantly associated with the level of NLR after RT, but not with the level of NLR before RT. In Cox multivariate model, post-RT NLR greater than 4 was independently correlated with worse DMFS (HR 1.37, 95% CI, 1.08-1.73), along with higher icT stage, ypT stage and ypN stage. The 5-year OS of patients with post-RT NLR > 4.0 was 83.2%, compared to 94.4% in post-RT NLR ≤ 4 patients (P < 0.001). Increased level of post-RT NLR (> 4.0) was more frequently developed after long-course RT (OR, 2.77, P = 0.032) or helical tomotherapy (OR, 1.29, P < 0.001). Local recurrence risk, pathologic complete response rate and neoadjuvant rectal score were not significantly differed by the level of NLR (all P > .05).Elevation of NLR after neoadjuvant RT is associated with increased risk of DM development and poor OS in LARC. Development of high NLR following RT is directly related to RT fractionation and delivery modality, and tumor characteristics. Incorporation of SCRT with 3D-CRT or active bone marrow sparing-IMRT may be a modifiable factor that can indirectly affect DMFS by means of attenuating NLR in LARC patients, which needs further investigations.

BrainWear: Longitudinal, objective assessment of physical activity in 42 High Grade Glioma (HGG) patients

Abstract Aims In patients with HGG, we know that QoL and physical function decline with progressive disease (PD) and fatigue is a strong predictor of survival in recurrent disease. Despite notable technical advances in therapy for in the past decade, survival has not improved. The role of physical function as a predictor of QoL, treatment tolerance and as an early indicator of worsening morbidity (e.g. tumour recurrence) is an area of growing importance. Recent advancements in wearable technology allow us the opportunity to gather high-quality, continuous and objective data BrainWear is a feasibility study collecting longitudinal physical activity (PA) data from patients with primary and secondary brain tumours and we hypothesise changes in PA over time, are a potentially sensitive biomarker for PD both at diagnosis and relapse. Method Here we show early analysis of this novel dataset of 42 HGG patients and will present: 1) feasibility and acceptability 2) how digitally captured PA changes through treatment and at PD/hospitalization 3) the correlation between patient reported outcomes (PRO) and PA data 4) how PA in HGG patients compares with healthy UK Biobank participants. PA data is collected via a wrist-worn accelerometer. Raw accelerometer data is processed using the UK Biobank Accelerometer Analysis pipeline in python 3.7, and evaluated for good quality wear-time. Overall activity is represented as vector magnitude in milligravity units(mg) and a machine-learning classifier classifies daily activity into 5 separate groups (walking, tasks-light, moderate, sedentary and sleep). Descriptive statistics summarise baseline characteristics and unadjusted mean used to present vector magnitude and accelerometer-predicted functional behaviours (in h/day) by age, sex, radiotherapy and weekend days. Mixed effect models for repeated measures are used for longitudinal data evaluation of PA. Results Between October 2018 and March 2021, 42 patients with a suspected HGG were recruited; 16 females and 26 males with a median age of 59. 40 patients had surgery and 35 patients had adjuvant primary radiotherapy, 23 of whom had a 6-week course. They have provided 3458 days of accelerometer data, 80% of which has been classified as good quality wear-time. There are no statistical differences in mean activity between gender, patients &amp;gt;60 years show statistical difference in time spent doing moderate activity compared to those &amp;lt;60 years, and there are significant differences in mean vector magnitude and walking between radiotherapy and non-radiotherapy days. In patients having a 6-week RT course, time spent in daily moderate activity falls 4-fold between week 1 and the second week following RT completion (70 minutes to 16 minutes). HGG versus healthy UK Biobank participants shows significant differences in all measures of PA. Conclusion Here we present preliminary analysis of this highly novel dataset in adult high grade glioma patients, and show digital remote health monitoring is feasible and acceptable with 80% of data classified as high quality wear-time suggesting good patient adherence. We are able to objectively describe how PA changes through standard treatments and understand the inter and intra-patient variation in PA, and whether there are correlates with patient-centred measures, clinical measures and early indicators of worsening disease. We will present further data on changes in PA prior to hospitalisation and at disease progression, and discuss some of the challenges of running a digital health trial. The passive and objective nature of wearable activity monitors gives clinicians the opportunity to evaluate and monitor the patient in motion, rather than the episodic snapshot we currently see, and in turn has the potential to improve our clinical decision making and potentially outcomes.