Late Radiation Research Articles

Artificial intelligence for diagnosis and prognosis prediction of natural killer/T cell lymphoma using magnetic resonance imaging

Accurate diagnosis and prognosis prediction are conducive to early intervention and improvement of medical care for natural killer/T cell lymphoma (NKTCL). Artificial intelligence (AI)-based systems are developed based on nasopharynx magnetic resonance imaging. The diagnostic systems achieve areas under the curve of 0.905-0.960 in detecting malignant nasopharyngeal lesions and distinguishing NKTCL from nasopharyngeal carcinoma in independent validation datasets. In comparison to human radiologists, the diagnostic systems show higher accuracies than resident radiologists and comparable ones to senior radiologists. The prognostic system shows promising performance in predicting survival outcomes of NKTCL and outperforms several clinical models. For patients with early-stage NKTCL, only the high-risk group benefits from early radiotherapy (hazard ratio= 0.414 vs. late radiotherapy; 95% confidence interval, 0.190-0.900, p= 0.022), while progression-free survival does not differ in the low-risk group. In conclusion, AI-based systems show potential in assisting accurate diagnosis and prognosis prediction and may contribute to therapeutic optimization for NKTCL.

Is there any radiation-induced brachial plexopathy after hypofractionated postmastectomy radiotherapy with helical tomotherapy?

Radiation-induced brachial plexopathy (RIBP) is one of the most concerning late radiation effects after hypofractionated postmastectomy radiotherapy (HF-PMRT) to the chest wall and regional lymph nodes. The purpose of this study was to investigate the RIBP events occurring in breast cancer patients after HF-PMRT using intensity-modulated radiation therapy (IMRT) by helical tomotherapy. Furthermore, the dosimetric parameters of the ipsilateral brachial plexus were reported. Breast cancer patients who underwent HF-PMRT using the IMRT via HT at our institute were included. In the first cohort, subjective RIBP symptoms were measured using a QuickDASH questionnaire, whereas objective RIBP events were assessed using a comprehensive physical evaluation in the second cohort. The ipsilateral brachial plexus from all eligible patients' treatment plans was contoured, and the dosimetric parameters were explored. From March 2014 to December 2022, 229 patients were enrolled; 107 and 72 individuals were in the first and second cohorts, respectively. The first cohort's median follow-up period was 27 months, and the second cohort was 31 months. In the first cohort, 80 patients (74.77%) had a normal function, 21 (19.63%) had a mild grade, and 6 (5.61%) had a moderate grade; no severe or very severe RIBP was observed. However, the comprehensive physical evaluation of the second cohort indicated no RIBP events. Dosimetric analysis revealed that the median maximum dose was 44.52, 44.52, and 44.60 Gy; the median mean dose was 33.00, 32.23, and 32.33 Gy; and the median dose at 0.03 cc was 44.33, 44.36, and 44.39 Gy for all patients, patients in the first and second cohort, respectively. Each dosimetric parameter was evaluated, and no statistically significant differences were detected. The absence of RIBP events supports the safety of employing HF-PMRT by HT for the chest wall and all regional lymph nodes. We propose that applying the ICRU Report 83 criteria for IMRT planning, which limit the maximum dose (107% of the prescribed dose) to less than 2% of the planning target volume and exclude the brachial plexus region from the maximal dose area, is a practical way to minimize the risk of RIBP from HF-PMRT.

ESHO 1–85. Hyperthermia as an adjuvant to radiation therapy in the treatment of locally advanced breast carcinoma. A randomized multicenter study by the European Society for Hyperthermic Oncology

BackgroundThe ESHO protocol 1–85 is a multicenter randomized trial initiated by the European Society for Hyperthermic Oncology with the aim to investigate the value of hyperthermia (HT) as an adjuvant to radiotherapy (RT) in treatment of locally advanced breast carcinoma. The trial is one of the largest studies of hyperthermia in radiotherapy but has not been previously published. Patients and methodsBetween February 1987 and November 1993, 155 tumors in 151 patients were included. Tumors were stratified according to institution and size (T2-3/T4) and randomly assigned to receive radiotherapy alone (2 Gy/fx, 5 fx/wk) to a total dose of 65–70 Gy, incl. boost, or the same radiotherapy followed once weekly by hyperthermia (aimed for 43 °C for 60 min). Radiation was given with high voltage photons or electrons. The primary endpoint was persistent complete response (local control) in the treated area. ResultsA total of 146 tumors in 142 patients were evaluable, with a median observation time of 19 (range 1–134) months. Seventy tumors were randomized to RT alone and 76 to RT + HT. Size was T4 in 92, and T2-3 in 54 tumors, respectively. The compliance to RT was good with all but 4 patients fulfilling the planned RT treatment. The tolerance to HT was fair, but associated with moderate to severe pain and discomfort in 15 % of the treatments. In 84 % of the heated patients a least one heat treatment achieved the target temperature, but the temperature variation was large. Addition of heat did not significantly increase the acute nor late radiation reactions.Overall, the 5-year actuarial local failure rate was 57 %. Univariate analysis showed a significant influence of hyperthermia (RT alone 68 % versus RT + HT 50 %, p = 0.04, and T-size (T4 75 % versus T2-3 36 %, p < 0.01). A Cox multivariate analysis showed the same factors to be the only significant prognostic parameters: hyperthermia (HR: 0.61 [0.38–0.98], and small tumor strata (HR: 0.46 [0.26–0.92]. Consequentially, more patients given RT + HT (36 %) survived without disease (DFS), than after RT alone (19 %), p = 0.021) ConclusionA randomized multicenter trial investigating the addition of a weekly hyperthermia treatment to radiotherapy of patients with locally advanced breast cancer significantly enhanced the 5-year tumor control and yielded more patients surviving free from cancer. The results substantiate the potential clinical benefit of hyperthermic oncology.

Early Postoperative Complications after Pelvic Exenteration

Background. Radiation therapy is an integral part of the treatment of most malignant neoplasms of the pelvic organs, which in 25–30% of cases can cause the development of late radiation complications; in addition, 2–8% of patients have severe complications with an outcome in fistulas of various localization. Also, tumors of this localization are prone to local-regional recurrence, which can be combined with late radiation injuries. One of the most radical, and, often, the only method of treating this extremely severe and prognostically unfavorable pathology is to perform evisceration of the pelvic organs; however, its implementation against the background of radiation damage to normal tissues, leading to a significant decrease in the reparative potential, inevitably leads to a high risk of postoperative complications.&#x0D; Methods. A retrospective analysis of early postoperative complications on the Clavien–Dindo scale was carried out in 136 patients after pelvic evisceration performed at the A.F. Tsyba MRSC in 2019–2021. All patients in the perioperative period underwent complex conservative therapy, including nutritional support.&#x0D; Results. Pelvic evisceration was performed due to the progression of the underlying disease in 57% of cases, in 29% — due to the development of severe late radiation injuries with an outcome in the fistula, in 14% — due to a combination of local recurrence of the underlying disease with radiation complications). Complications of grade I on the Clavien–Dindo scale were noted in 50%; II — in 20.5%; III — in 3.6%; grade IV — in 3%. There were no cases of postoperative mortality.&#x0D; Conclusions. Conducting active preoperative preparation of patients aimed at correcting anemia, dysproteinemia, pain syndrome, etc.; as well as modifying surgical techniques and improving the management tactics of postoperative patients can minimize the risk of postoperative complications in patients after pelvic evisceration.

Determining the Appropriateness and Acceptability of a Reduced Postradiotherapy Surveillance Practice in Breast Cancer Patients: Results of a Longitudinal Observational Study

Postradiotherapy surveillance, which aims to detect and treat radiation injury, is important from the patient’s perspective, but also from the radiation oncologist’s perspective. Unfortunately, patient nonattendance increases over the course of five years. The aim of the study was to investigate the appropriateness and acceptability of reduced versus usual (conventional) postradiotherapy surveillance in breast cancer patients. A total of 192 consecutive patients with curatively irradiated breast cancer from two selected treatment years were included in our study, of whom 65 were offered six (after three months, 12 months, 24 months, 36 months, 48 months, and 60 months) and 127 were offered four follow-up appointments (after three months, 12 months, 36 months, and 60 months). Their patient-, tumour- and treatment-related characteristics were analysed, as well as follow-up events and attendance rates. The reduced four-meeting surveillance practice shows similar results to the traditional six-meeting practice in terms of appropriateness and acceptability, with significantly higher attendance rates at 36 and 60 months (p=0.014 and 0.013, respectively) when the individual moments are compared on a one-to-one basis. The patient-, tumour-, and treatment-related variables examined did not show an effect on the attendance rate. There was also no significant difference between the two cohorts in the detection of follow-up events (such as recurrence) and late radiation effects. In conclusion, this retrospective study provides scientific support for the trend towards a risk-adjusted, reduced surveillance practice in radiation oncology. In particular, four postradiotherapy follow-up visits seem to be appropriate and accepted in breast cancer patients after curative postoperative breast irradiation. This reduced postradiotherapy surveillance practice has the advantage of saving time for the patient and resources for the healthcare system without compromising quality; it could also improve patient participation. We, therefore, recommend it as an appropriate standard for breast cancer patients.

Hyperbaric oxygen therapy for the treatment of the late effects of radiotherapy [Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Lin ZC, Bennett MH, Hawkins GC, Azzopardi CP, Feldmeier J, Smee R, Milross C. Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev. 2023;8(8): CD005005. DOI: 10.1002/14651858.CD005005.pub5

Hyperbaric Oxygen Therapy for Management of Late Radiation Toxicity—A Honey of a Trial?

Hyperbaric Oxygen Therapy for Management of Late Radiation Toxicity—A Honey of a Trial?

Postoperative Intensity Modulated Radiotherapy for Acinic Cell Parotid Carcinoma in Childhood- A Clinical Case from our Practice with Literature Review

Malignant parotid tumors in childhood are extremely rarely diagnosed diseases. Due to the rare incidence, there is no consensus on their complex treatment, as well as on the application of postoperative radiation therapy (RT). We present a clinical case of acinic cell parotid carcinoma in a 12-year-old girl, against the background of which we emphasize the optimal complex therapeutic approach. Despite radical facial nerve-sparing parotidectomy in pT2N0 acinic cell parotid carcinoma, due to the two pathohistological negative factors/two foci with vascular tumor invasion and the close proximity of the resection line to the preserved facial nerve, we conducted postoperative adjuvant RT. Due to the risk of late radiation reactions of normal tissues and organs after RT in childhood, intensity modulated radiation therapy (IMRT) with lower radiation doses in the target volumes was performed. Active surveillance and follow-up imaging studies are required for early diagnosis of possible recurrence or distant metastases.

The AsiDNA™ decoy mimicking DSBs protects the normal tissue from radiation toxicity through a DNA-PK/p53/p21-dependent G1/S arrest.

AsiDNA™, a cholesterol-coupled oligonucleotide mimicking double-stranded DNA breaks, was developed to sensitize tumour cells to radio- and chemotherapy. This drug acts as a decoy hijacking the DNA damage response. Previous studies have demonstrated that standalone AsiDNA™ administration is well tolerated with no additional adverse effects when combined with chemo- and/or radiotherapy. The lack of normal tissue complication encouraged further examination into the role of AsiDNA™ in normal cells. This research demonstrates the radioprotective properties of AsiDNA™. In vitro, AsiDNA™ induces a DNA-PK/p53/p21-dependent G1/S arrest in normal epithelial cells and fibroblasts that is absent in p53 deficient and proficient tumour cells. This cell cycle arrest improved survival after irradiation only in p53 proficient normal cells. Combined administration of AsiDNA™ with conventional radiotherapy in mouse models of late and early radiation toxicity resulted in decreased onset of lung fibrosis and increased intestinal crypt survival. Similar results were observed following FLASH radiotherapy in standalone or combined with AsiDNA™. Mechanisms comparable to those identified in vitro were detected both in vivo, in the intestine and ex vivo, in precision cut lung slices. Collectively, the results suggest that AsiDNA™ can partially protect healthy tissues from radiation toxicity by triggering a G1/S arrest in normal cells.

Examining patient-reported late toxicity and its association with quality of life and unmet need for symptom management among nasopharyngeal cancer survivors: a cross-sectional survey.

Alongside the improved survival of nasopharyngeal cancer (NPC), late radiation toxicities are alarmingly hampering survivors' quality of life. A patient-reported symptom burden survey is lacking to address the unmet need for symptom management among local NPC survivors. A single-center cross-sectional survey was conducted on 211 NPC survivors who had completed radiation therapy for three to 120 months. We employed the Chinese version M. D. Anderson Symptom Inventory - Head & Neck Module (MDASI-HN-C), Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN-C), and a question extracted from the Cancer Survivors' Unmet Needs Measure (CaSUN). Two hundred valid responses were collected. Participants suffered from at least four moderate to severe symptoms (mean = 4.84, SD = 4.99). The top five severe symptoms were dry mouth, mucus problems, difficulty swallowing or chewing, teeth or gum problems, and memory problems. MDASI-HN-C subscales were negatively correlated with the physical, emotional, functional, and HN-specific domains of the FACT-HN-C. The unmet need for symptom management was positively associated with symptom burden, either general symptoms (Adjusted odds ratio [ORadj] = 1.566, 95% CI = 1.282 - 1.914, p < 0.001) or top-5 symptoms (ORadj = 1.379, 95% CI = 1.185 - 1.604, p < 0.001), while negatively associated with post-RT time (ORadj = 0.981, 95% CI [0.972, 0.991], p < 0.001). Virtually all NPC survivors suffer from late toxicities, which interplay with survivors' perceptions intricately to affect their unmet needs for symptom management. Personalized supportive care strategies with regular assessments and stratifications are warranted.

Safety, Effectiveness and Pitfalls of Carbon Dioxide Routine Use as a Contrast Agent for Endovascular Abdominal Aortic Repair

Despite the evidence of good performance, carbon dioxide (CO2) routine employment as a contrast agent for endovascular procedures is far from being adopted with its use currently limited to patients with renal impairment and known allergy to iodinated contrast medium (ICM). The purpose of our study is to evaluate the safety and effectiveness of CO2 guided endovascular abdominal aortic aneurysm repair (EVAR) in a standard population and to assess the rationale for a future widespread use. We retrospectively collected data of every patient who underwent CO2 guided standard EVAR from September 2020 to May 2021 and compared them with the data of every patient who underwent EVAR using ICM from December 2019 to August 2020 in our unit. The selection of the contrast medium was not based on any preoperative factor as the contrast medium was routinely used in every patient in both periods. The primary end point of the study was the technical success rate. Secondary end points were the early and late complication rates, radiation exposure and renal function impairment. 49 patients underwent ICM guided EVAR and 52 patients underwent CO2 guided EVAR in our unit in the time frames specified above. The technical success rate was 100% in both groups with no accidental coverage of any target vessel. Intraoperative endoleaks were observed in 14% of ICM patients and 25% of CO2 patients. The radiation exposure was higher in the CO2 group if compared to the ICM group (311.48 vs. 159.86 median mGy/cm2 - P<0.001). The incidence of postoperative acute kidney injury was low and similar in the 2 groups. No significant worsening over time of the renal function has been reported in both groups. EVAR can be safely performed under CO2 guidance without the integration of any quantity of ICM but with an increase in radiation exposure. The nephroprotective role of CO2 guided EVAR in a standard population is unclear and the same role in renal impaired patients should be validated with further studies on selected populations.

RADT-31. OPTIMAL TIMING OF CHEMORADIATION AFTER RESECTION OR BIOPSY OF GLIOBLASTOMAS: A NATIONWIDE POPULATION-BASED STUDY

Abstract BACKGROUND The optimal time interval of concomitant chemoradiotherapy (CCRT) after surgery for newly diagnosed glioblastoma (GBM) patients remains controversial. This study was aimed to assess whether the interval between surgery and CCRT leads to a survival difference. METHODS Using the Korean National Health Insurance Research Database, 3,586 patients diagnosed with GBM in South Korea from 2008 to 2021 were retrospectively reviewed. The eligibility criteria were GBM-diagnosed patients who underwent surgical resection or biopsy and received CCRT (with temozolomide (TMZ)) within 6 weeks thereafter. Patients were divided into two groups based on interval between surgery and CCRT initiation: early radiotherapy (RT) within 21 days and late RT &amp;gt; 21 days. Patients were separately examined by the type of surgery – biopsy alone or resective surgery. Overall survival (OS) was estimated using the Kaplan-Meier method and log-rank tests. Univariable and Multivariable Cox regression analyses were performed to assess the impact of the covariables on OS. RESULTS The median OS for early RT group was 20.47 months compared to 17.94 months of late RT group (Log rank P value of 0.0002). Early RT was associated with prolonged OS in multivariable analysis adjusting age, sex, length of stay in hospital after surgery, and the procedure type of biopsy or tumor resection. On the contrary, subgroup analysis showed that patients who received early RT after biopsy showed higher OS than the patients who received late RT (15.93 months vs. 11.83 months). CONCLUSION Patients who received CCRT after 21 days of operation showed better OS than those with earlier CCRT initiation. In contrast, in the group patients who received biopsy alone showed better outcomes when started RT within 21 days. This result suggests that optimal timing of initiation of CCRT after surgery for glioblastoma may be different according to the remnant tumors.

What are the benefits and harms of hyperbaric oxygen therapy (HBOT) for people with late radiation tissue injury?

What are the benefits and harms of hyperbaric oxygen therapy (HBOT) for people with late radiation tissue injury?

A Needs Assessment Exploring Radiation Oncology Nursing Confidence in Caring for Patients with Acute and Late Radiation Therapy Effects.

Registered Nurses (RN) have a critical and growing role in providing RO patient care. Moskalenko et al. published the first RO nursing needs assessment in the USA in 2021, reporting that RO nurses lacked standardized, structured education and certification programs for onboarding and continuing education. Herein, we report RN confidence in providing RO survivorship care. With permission from Moskalenko et al., an adapted version of their needs assessment survey was administered to RNs at a single academic medical center RO department in an IRB-exempt study. This survey used a Likert-type scale ranging from 1 (Not At All Confident) to 5 (Extremely Confident) to assess confidence across the following clinical domains: managing acute and late radiation effects, providing patient education regarding imaging, external beam radiation therapy (EBRT), high-dose rate brachytherapy (HDR), concurrent systemic therapy, anesthesia recovery, radiation safety, and general cancer knowledge. RNs in RO were surveyed with a 100% (n = 14) response rate. Respondents were 61.5% oncology-certified nurses (OCN). 84.6% attended schools without affiliated RO departments or RO clinical experiences. 69.2% reported ≥5 years of oncology experience, and 45% had ≥5 years of RO experience. All RNs reported performing patient education. RNs expressed a high degree of confidence in managing triage phone calls (median 4, IQR [4-5]). RNs had moderate confidence in their general understanding of radiation (3 [3-4]), RO care team responsibilities (3 [3-4]), radiation treatment planning (3 [2-4]) and set up (3 [2-4]). RNs expressed the lowest confidence in regulatory aspects of radiation safety (2.5 [2-3]). RN confidence with patient education included the following domains: CT (3 [3-4]), MRI (3 [3-4]), PET (3 [3-4]), simulation (3 [2-4]), EBRT (3 [3-4]), anesthesia recovery (3 [3-4]), HDR (2.5 [1-5]), medication side effect management (4 3-4]), hormone treatments (3 [2-4]), and concurrent chemoradiation (3 [3-4]). Regarding acute toxicity management, RNs reported highest confidence with prostate/genitourinary (4 [3-4]), lung (4 [3-4]), and sarcoma cancers (3.5 [2-4]); with lower scores across hematologic (2.5 [2-4]) and pediatric cancers (2 [1-4]). Regarding late side effect management, the highest scores were observed among prostate/genitourinary (3 [2-4]), sarcoma (3 [2-4]), and breast (3 [2-3]) cancers; with comparatively lower scores for skin (2 [2-4]), CNS (2 [2-3]), GI (2 [2-3]), hematologic (2 [2-3]), and pediatric cancers (2 [1-2]). While this single-site pilot project is limited by small sample size, it highlights the need for a formalized curriculum, scope of practice, and credentialing for RO nurses. These data can help to target education needs while guiding curriculum development.

Outcomes and Toxicities in Patients with Diffuse Large B-Cell Lymphoma of the Gastrointestinal Tract.

Diffuse large B-cell lymphoma (DLBCL) involving the gastrointestinal (GI) tract is rare and long-term outcomes are not well defined. Combined modality therapy (CMT) with radiotherapy (RT) in addition to systemic therapy in this setting is not commonly pursued. We aim to characterize outcomes in patients with GI DLBCL treated with systemic therapy, with or without RT. Patients diagnosed with DLBCL of the GI tract (with or without mesenteric involvement) treated at a single institution from 1988-2022 were retrospectively reviewed on an IRB-approved protocol. Clinical and treatment data were collected including adverse events (AE; acute vs late defined as before or 4 weeks after therapy end). Kaplan-Meier and Cox regression models were used to estimate survival. Of 207 patients, 62% were male and median age at diagnosis was 63 (IQR 52-73). Gastric involvement was most common (n = 130, 63%), followed by small intestines (n = 48, 23%) and colon/rectum (n = 24, 12%). Most presented with early-stage disease (n = 124, 60%), with a median IPI score of 1. All patients received chemotherapy. Of 182 treated with CHOP/EPOCH, 36 (20%) were treated in the pre-rituximab era while 146 (80%) received rituximab. 66 patients (32%) were treated with RT, 89% as part of first line CMT. 50 cases (76%) received consolidative RT, while 10 (15%) targeted residual gross disease and 4 (6%) targeted distant sites. Median dose and fractionation were 36Gy (IQR 30.6-39.6) in 18 fractions (IQR 17-22). Over half (n = 132, 64%) developed grade 3+ acute chemotherapy AEs, and the most common were anemia (n = 64), febrile neutropenia (n = 40), and neutropenia (n = 20). Grade 3+ late chemotherapy AEs occurred in 14 patients (7%). Acute grade 3+ radiation AEs were uncommon (n = 2, 3%; colitis, emesis). No grade 3+ late radiation AEs were noted. Median follow-up was 46 months (IQR 16-97). 169 (81.6%) had a complete response (CR), with 154 (91%) after first line chemotherapy, 9 (5%) after second line, and 6 (4%) after RT. CR was defined by PET (62%), endoscopy (22%), CT (9%), or other methods (7%). The 5-year progression-free survival for those treated with one line of chemotherapy with or without RT was 95%. Median overall survival (OS) was not reached. Improved OS was associated with early-stage disease (p = 0.003), low IPI (p = 0.001), fewer chemotherapy lines (p<0.001), and CR (p<0.001). OS did not differ by gender, age, immunophenotype, GI site, SUVmax, or RT. Patients with early stage DLBCL treated with RT in the post-rituximab era received fewer chemotherapy cycles compared to those treated without RT (p = 0.02; median of 4 (IQR 3-6) vs 6 cycles (IQR 4-6)), with no OS difference. GI DLBCL patients have favorable outcomes after CMT with minimal late toxicity. CMT with RT to the GI tract is well tolerated with no OS difference compared to chemotherapy alone, and may mitigate risks from additional chemotherapy cycles for selected early-stage patients.

Proton Radiation Therapy for Stage IIA/IIB Testicular Seminoma.

Testicular seminoma affects young men and is associated with very favorable prognosis. The evolution in treatment paradigm has focused on minimizing acute and especially late toxicities. Following orchiectomy, while surveillance is favored in Stage I patients, radiotherapy (RT) is a standard treatment option for de novo or relapsed stage IIA or select non-bulky stage IIB disease. Despite low doses, standard RT fields to paraaortic and pelvic lymphatics using x-rays exposes a large volume of uninvolved normal tissue/viscera to excess dose. This young patient population is especially vulnerable to risks of late RT toxicities including secondary malignancy. Proton beam therapy (PBT) has dosimetric advantage over x-ray-based RT due to lack of exit dose, and comparative dosimetric/modeling studies show significant sparing of uninvolved abdominal/pelvic organs. However, there is scant reported clinical data at this time for PBT. We review our early institutional outcomes with PBT for testicular seminoma. Single institution retrospective review from a tertiary care center of patients treated with PBT from 2013-2022 for testicular seminoma. Recurrence free (RFS) and overall survival (OS) were calculated from the completion of PBT. Toxicities were graded (Gr) using CTCAE v5.0. Four patients underwent PBT, median age 39 (range 36-47). All were Stage I at diagnosis (pT1b n = 3; pT2 n = 1) and were treated for recurrent stage II disease (IIA n = 3; IIB n = 1) at a median of 34 months from orchiectomy (range 3 - 74 months). Nodal extent included 2 with multiple paraaortic nodes, 1 with solitary paraaortic node and 1 with solitary pelvic node. PBT was delivered with pencil-beam scanning, treating paraaortic + ipsilateral pelvic fields (20 Gy in 10 fractions), then sequential boost to involved nodes (10 -16 Gy in 5-8 fractions). Typically, PA or posterior oblique fields were used to minimize dose to out-of-field abdominal/pelvic viscera. Treatment was well tolerated with minimal acute toxicities: fatigue Gr 1 (n = 3), nausea Gr 1 (n = 3). No Gr 2 or higher acute toxicities or significant late toxicities were observed. At median follow up of 30 months (range 3 - 54), no recurrences were observed, and RFS and OS were 100%. Two patients are without evidence of disease > 4 years post-treatment. In this case series, PBT for retroperitoneal and pelvic metastases in Stage IIA/IIB testicular seminoma was associated with oncologic efficacy with minimal toxicity. PBT reduces unnecessary dose to abdominal/pelvic organs compared to x-ray techniques, which is advantageous in young patients who have anticipated long-term survival. This is one of the few series reporting clinical outcomes of PBT in the management of seminoma. Randomized comparisons with x-ray approaches are impractical given the relatively low volume of patients receiving RT in modern seminoma management, so it is essential to report and track longitudinal outcomes across institutions to validate this approach.

Outcomes for Patients with Head and Neck Sarcoma Treated Curatively with Radiation Therapy and Surgery

Soft tissue sarcomas (STS) of the head and neck are rare and diverse entities that are challenging to manage. Definitive treatment requires surgery, often with radiation therapy (RT). We sought to describe the outcomes of patients treated curatively with surgery and RT for head and neck STS. We performed a retrospective review of patients treated at a tertiary cancer center for non-metastatic STS of the head and neck between 1968 and 2020; over half were treated in the modern era defined as 2005 or after. Patients with rhabdomyosarcomas or cutaneous angiosarcoma were excluded. The Kaplan-Meier method was used to estimate actuarial overall survival (OS), disease-specific survival (DSS) and local control (LC). Multivariable analyses (MVA) were conducted using Cox proportional hazards model. Median follow-up was 82 months. Of the 192 patients, the majority were male (n = 111, 58%), White (n = 158, 82%), and median age was 49.5 [IQR 32.5-64]. The highest proportion of tumors were in the neck (n = 50, 26%), paranasal sinuses (n = 36, 19%), or face (n = 23, 12%). The most common histology was sarcoma, not otherwise specified (n = 44, 23%), followed by undifferentiated pleomorphic sarcoma (n = 32, 17%), and neurogenic sarcoma (n = 15, 8%). Most patients were treated with postoperative RT (n = 134, 70%). Patients treated with preoperative RT were older (median 56.5 yrs vs post-op 44 yrs, p = 0.009). Post-op RT doses were higher (median 60 Gy, pre-op 50 Gy, p<0.001), and margins were more likely to be negative in those treated with pre-op RT (n = 39, 67%, post-op 69, 51%, p = 0.02). 5-year LC, DSS, and OS for the entire cohort was 76% (95% CI 69-82), 74% (67-80), and 71% (64-77), respectively. LC was not affected by treatment sequence (pre-op RT 78% (63-88), post-op RT 75% (66-82), p = 0.48). Patients with negative margins had improved 5-yr LC (86% (77-92), positive/uncertain 65% (53-74), p = 0.003). On MVA, positive/uncertain margin was the only variable associated with LC (HR 2.54 (1.34-4.82), p = 0.004). Poorer 5-yr DSS was associated with higher grade (grade 3 75% (63-84), grade 1-2 89% (75-94), p = 0.02), and treatment era (pre-2005 68% (57-76), on/after 2005 80% (70-87), p = 0.04). These both remained significant on MVA (grade 3 HR 2.39 (1.07-5.36), p = 0.034; pre-2005 HR 2.31 (1.03-5.21), p = 0.043). Sixteen patients (8%) developed a late RT toxicity, including fibrosis (n = 4, 2%), necrosis (osteoradionecrosis n = 2, brain necrosis n = 1, soft tissue necrosis n = 1), and eye dryness (n = 2, 1%). Neither the timing of RT nor dose was found to be associated with developing a late RT toxicity. Head and neck STS continues to have relatively poorer local control than STS of the trunk or extremities. Timing of RT did not impact oncologic or long-term RT-related toxicity outcomes. However, more data are needed to ascertain whether preoperative RT may impact acute surgical toxicities. These data contribute to multidisciplinary care planning for patients with STS in these challenging anatomic locations.

Multi-Institutional Phase II Trial Using Dose Escalated Five Fraction Stereotactic Partial Breast Irradiation (S-PBI) with GammaPodTM for Early-Stage Breast Cancer

We report on our early experience of a multi-institutional phase II study of dose escalated five fraction stereotactic partial breast irradiation (S-PBI) for early-stage breast cancer after partial mastectomy using the GammaPodTM stereotactic radiation system. Patient eligibility included DCIS or invasive epithelial histologies, AJCC clinical stage 0, I, or II with tumor size < 3 cm, and negative margins. Prior safety of Phase I dose escalation has been reported. Dose was 40 Gy delivered in 5 fractions to the CTV, and minimum dose 30 Gy in 5 fractions to the PTV. CTV margin was 1 cm and PTV margin 3 mm. For PTV cavities larger than 100cc, dose was reduced to 35Gy in 5 fractions to the CTV and 30 Gy in 5 fractions to the PTV. Primary endpoint of the study is to determine the 3-year patient global cosmesis score (4-point scale excellent, good, fair, or poor) and adverse cosmesis using a dose escalated approach with smaller PTV margins than conventional methods. Both patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Treatment related toxicity was graded using the NCI version 4.0 and RTOG/EORTC late radiation scale. From 3/2019-10/2021, 74 patients were treated respectively. Of these, 38 were treated to 40Gy and 36 were treated to 35 Gy. Median follow up (f/u) was 24 months (mo), range (r) 3-39mo. Median age was 63 years (r 43-77). Histology included 28 DCIS, and 46 invasive carcinomas. 45/46 invasive tumors were ER+. 60/74 (81%) patients received endocrine therapy, and 7/74 patient received chemotherapy. There were 221 acute grade 1 toxicities, and 28 Grade 2 toxicities. No grade 3 or higher acute toxicities were reported (< 90 days). The most common Grade 2 toxicities were radiation dermatitis (10), breast pain (8), blister (4), skin infection (2), nipple discharge (2), and fatigue (2). In the late period, there were 54 Grade 1 late toxicities, 4 Grade 2 late toxicities, and no Grade 3 or higher late toxicities. Grade 2 toxicities included fibrosis (2), and pain (2). Two patients developed grade 1 asymptomatic nonpalpable fat necrosis both diagnosed at 12 months after radiation treatments. The most common grade 1 late toxicities were breast pain (14), hyperpigmentation (8), fibrosis (10), and fatigue (5). Physicians scored cosmesis excellent or good 70/73 (95.8%), 58/60 (96.7%), 36/36 (100%),17/17(100%) respectively at baseline, 12 months, 24 months, and 36months post SBRT, while patients scored the same periods 62/71 (83.7%), 53/59 (89.8%), 33/36 (91.6%), 17/18 (94.4%). There have been no reports of disease recurrences. Results at 24-month median follow-up, of our dose escalated stereotactic partial breast 5 fraction regimen, has low acute and late toxicity, while maintaining high proportion of excellent/good cosmetic outcomes. Continued analysis of all cohorts is in progress. gov identifier is NCT03581136.

Stereotactic Ablative Radiotherapy Boost to Bladder Tumor for Bladder Preservation in Patients with Muscle-Invasive Bladder Cancer

Previous studies showed that selective bladder-sparing approach using TMT is an established therapy of MIBC with outcomes that are comparable to those of radical cystectomy. However, it has been shown that the 5-year local recurrence in the bladder is greater than 40% after TMT. One of the possible reasons was that the RT dose to the bladder tumor or tumor bed was insufficient. Thus, we assessed the effectiveness and safety of Stereotactic Ablative Radiotherapy (SABR) boost to bladder tumor or tumor bed for patients with muscle invasive bladder cancer (MIBC). A total of 59 consecutive patients with cT2-4 bladder cancer underwent transurethral resection of bladder tumor (TURBT). TURBT was visibly complete in 25 cases. Patients received SABR to the tumor or tumor bed in the bladder followed by conventionally fractionated RT (CFRT) to pelvis and total bladder with concomitant weekly radio-sensitizing chemotherapy. During SABR intravesical installation of isovolumetric saline through urinary catheter ensured adequate bladder filling. Response rate was assessed by cystoscopic evaluation and pelvic MRI or CT. Toxicities were reported per the RTOG acute and late Radiation Morbidity Scoring Schema. The median age of all patients was 76 years (35-90 years). All patients completed SBRT boost and 61% patients received concurrent Gemcitabine chemotherapy. After a median follow-up time of 28 months, the rate of local control (LC) at 3 years was 90.0%. The overall survival (OS) and cancer-specific survival (CSS) rates at 3 years were 61.6% and 77.5%, respectively. Of the surviving patients, 84.4% have a disease-free and functioning bladder. Acute grade 3 gastrointestinal (GI) or genitourinary (GU) toxicities occurred in only 1.7% of the patients. Late grade 3 GU toxicity occurred in 5.1% of the patients. No patients experienced grade 4 GI or GU toxicities. SABR boost followed by chemoradiation to the pelvis was found to be a well-tolerated and effective treatment for MIBC patients who are either not candidates for cystectomy or who desire bladder preservation. Randomized study is required to further evaluate this novel tri-modality treatment paradigm.

Immediate and long-term results of radiation therapy in combination with capecitabine and oxaliplatin in the treatment of patients with asquamous cell carcinoma of the anus

Introduction. The current standard of care is concurrent radiation therapy (RT) and chemotherapy with mitomycin or cisplatin in combination with fuoropyrimidine drugs. One possible option for effective chemotherapy regimens with a lower toxicity is the combination of oxaliplatin and capecitabine with RT. The purpose of the study: a retrospective evaluation of the results of combined treatment of 74 patients with squamous cell carcinoma of the anus (SCCA) with the use of oxaliplatin and capecitabine. Material and Methods. The study included 74 patients (men – 12.2 %, women – 87.8 %) with stage I–III SCCA. All patients underwent megavolt photon RT (2×25), a cumulative dose of 50 Gy and a boost of 10 Gy to the anal canal. From days 1 to 14 and from days 22 to 36 of RT, capecitabine was administered orally at a dose of 825 mg/m2 twice a day in combination with intravenous administration of oxaliplatin 50 mg/m2 on days 1, 8, 22, and 29 of RT. If a residual tumor 6 months after completion of chemoradiotherapy was found, patients underwent surgery. Results. All 74 patients underwent RT with a cumulative dose of 60 Gy. Chemotherapy, according to the protocol, was completed in 58 (78.4 %) patients. Grade 3-4 toxicity was noted in 11 (14.9 %) patients. In 64 patients (86.5 %), a complete clinical response was registered. At least one late radiation side effects according to the RTOG (LENT SOMA) scale was noted in 48 (98.0 %) patients, including grade 3-4 complications in 12 (24.5 %) patients. With a median follow-up of 40 months (3-82) cumulative three-year local recurrence rate, overall and relapse-free survival were 15.3 ± 4.5 %, 73.7 ± 5.7 % and 53.5 ± 6.4 %, respectively. Conclusion. Combined treatment of SCCA, based on the combination of RT with chemotherapy with oxaliplatin and capecitabine, is feasible and has acceptable acute toxicity. Additional clinical studies are needed using this chemotherapy regimen in combination with modern RT techniques.