Radiation Therapy Oncology Group Criteria Research Articles

Indian Data on the Response of Positive Pelvic Lymph Nodes in Carcinoma Cervix Patients Treated with Simultaneous Integrated Boost Using Volumetric Modulated Arc Radiation Therapy

Abstract Background The percentage of pelvic lymph node (LN) positivity in cervical cancer patients varies from 19% in early stages to 68% in advanced cases. Thirty-three percent of patients will develop recurrence within 2 years following therapy, and 5-year relative survival for patients with affected regional LNs is 57%. Hence, pelvic LNs need to be included in the definitive plan of radiation treatment for better disease control and longer survival. With conventional radiation therapy, dose escalation was not possible because of small bowel constraints. With higher conformity of intensity-modulated radiotherapy technique, doses to pelvic and abdominal organs can be minimized. The added advantage of simultaneous integrated boost (SIB) is that high dose per fraction is delivered to the gross disease and low dose to the microscopic disease, thereby reducing the total treatment time and improving the therapeutic ratio. Materials and Methods Forty-one patients presenting to the Department of Radiation Oncology, between January 2016 and June 2017, with newly biopsy-proven carcinoma cervix Stage IB to IVA were enrolled in the study, and all the investigations were performed. The radiation dose was delivered using volumetric modulated arc therapy plan according to the dose of 5,000 cGy in 25 fractions to the whole pelvis and 5,500 cGy in 25 fractions to the involved nodes at 220 cGy per fraction using SIB along with weekly cisplatin at 40 mg/m2. After completion of external beam radiation, all the patients received three fractions of brachytherapy to a total dose of 21 Gy. Acute toxicities were assessed using Radiation Therapy Oncology Group criteria. At 3 months after completion of treatment, all the patients were followed up with diffusion-weighted magnetic resonance imaging of abdomen and pelvis to assess the response after 3 months. Results Of 41 carcinoma cervix patients with significantly positive LNs treated with SIB VMAT, 9.8% of the patients (4 patients) had residual nodal disease and 87.8% of the patients (36 patients) had a complete response, and 19.5% (8 patients) had residual disease of primary and 78% (32 patients) had a complete response at 3 months after completion of treatment with only grade I and grade II toxicities. Conclusion Treatment with SIB VMAT in carcinoma cervix patients with significant pelvic LNs shows a very good response with acceptable acute toxicities. But longer follow-up period is required to see if this response translates into better disease-free survival and overall survival.

Dose-Escalated Intensity-Modulated Radiotherapy for the Management of Locally Advanced Cervical Cancer.

ObjectiveIn this study, we aimed to assess the response and toxicity related to dose escalation in external beam radiation therapy (EBRT) using intensity-modulated radiation therapy (IMRT) with weekly concurrent cisplatin followed by de-escalated brachytherapy (BT) in locally advanced carcinoma cervix of International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIB-IIIC1.Materials and methodsFifty-two patients diagnosed with cervical cancer FIGO 2018 stage IIB-IIIC1 were treated with curative intent from November 2019 to October 2021. The dose of 50 Gy was prescribed for the primary tumor volume and elective pelvic nodal volume followed by a primary boost to a dose of 20 Gy. Gross lymph node (LN) of size >1 cm after EBRT completion received a sequential nodal boost of 10 Gy. All patients received concurrent cisplatin to a dose of 40 mg/m2 for a total of five to six weekly cycles. All patients received two fractions of BT to a dose of 6 Gy after EBRT completion. Radiation-induced acute toxicities were graded according to the Radiation Therapy Oncology Group (RTOG) criteria and hematologic toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v4.0).ResultsA median follow-up of six months was available for the 40 eligible patients. All patients tolerated treatment with an acceptable toxicity profile. Grade III dermatitis, grade III gastrointestinal (GI) toxicity, and grade III genitourinary (GU) toxicity were seen in three (7.5%), six (17.5%), and three patients (7.5%) respectively. Grade I anemia was evident in all patients. At six months after EBRT completion, 37 patients (92.5%) had a complete response and only three patients (7.5%) had residual disease.ConclusionBased on our findings, patients with cervical cancer treated with dose-escalated IMRT have a satisfactory outcome with reasonably low levels of treatment-related acute GI and GU toxicities. The findings of the present study endorse the notion that the application of a high dose of external radiation to the pelvis by IMRT technique with image-guided delivery could be an acceptable alternative to the standard-dose management schedule.

The Effectiveness of a Novel Skin Barrier Protectant in the Management of Acute Radiation Dermatitis: A Case Series.

Acute radiation dermatitis (ARD) is a frequent adverse effect in patients with cancer undergoing radiotherapy (RT). The aim of this case series is to evaluate the effect of a novel skin barrier protectant in patients with ARD. The skin barrier protectant was used in four patients with different cancer types undergoing RT at two clinical sites. All patients received the standard institutional skincare alongside the novel skin barrier protectant. The skin reactions were evaluated by an RT nurse using the modified version of the Radiation Therapy Oncology Group criteria. At the final RT session, three of four patients developed erythema with or without dry desquamation. One patient presented only a minor patchy moist wound. Overall, the pain and pruritus due to ARD was low or nonexistent. No adverse events related to the skin barrier protectant were reported. This case series demonstrates the beneficial effects and safety of the novel skin barrier protectant in the management of ARD in patients with cancer of different etiologies. These results lay the foundation for future studies with larger, more homogeneous patient populations; a well-defined application scheme; and a stricter study design.

Radiation Therapy for Prostate Cancer Using HYpofractionation Directed by UltraSound (RAPHYDUS): A Brazilian Public Health Care System Study

PurposeThis study evaluated the toxicity associated with a short course dose-escalated hypofractionated radiation therapy (HFRT) using image guided RT with or without androgen suppression therapy in patients with prostate cancer. Methods and MaterialsThis single-center prospective observational study included 132 patients with prostate cancer from 2016 to 2020. Patients received HFRT using image guided RT (84%) with 3-dimensional (91%) or intensity modulated RT (9%). Total prescribed doses were 66 Gy (63%), 63 Gy (12%), and 60 Gy (24%) in 22, 21, or 20 daily fractions depending on organ-at-risk dose constraints. Acute toxicity was scored using Radiation Therapy Oncology Group criteria and the international prostate symptom index. The expanded prostate cancer index composite questionnaire was used to collect quality of life data (ranging from 0-100). ResultsThe study population consisted of 111 patients who completed RT during a period of 3 years. The risk groups were as follows: low risk (12%), intermediate (32%), and high (56%). None of the patients had suspicious lymph nodes. Ninety percent received androgen suppression therapy. Maximum acute genitourinary and gastrointestinal toxicity peaked at grade 3 in 4 of 111 evaluated patients (4%) and at grade 2 in 7 of 111 evaluated patients (8%), respectively. The average international prostate symptom score increased from 4.8 at pretreatment to 14.0 during week 4 and normalized (5.7) 3 months after treatment completion. ConclusionsThe current HFRT dose-escalation trial has demonstrated the feasibility of administering 66 Gy in 22 fractions with low acute gastrointestinal and genitourinary toxicities. Further follow-up will report late toxicities and outcomes.

Implementation of Locoregional Adjuvant Radiotherapy for Breast Cancer in a Rural Healthcare Region: Toxicity Outcomes in the Initial Cohort.

The aim of this study was to analyze the toxicity of locoregional adjuvant breast cancer radiotherapy after implementation of this service in a rural healthcare region with long travel distance. This was a retrospective single-institution analysis of 87 consecutive female patients (the initial cohort), managed with conventionally fractionated 3-D conformal radiotherapy with or without boost, including both post mastectomy and breast conservation scenarios. Treatment was administered in line with comprehensive national guidelines. Intensity-modulated techniques were not utilized. The median follow-up time was 4 years. None of the patients developed any grade IV side-effects. According to Radiation Therapy Oncology Group criteria, acute grade 2b or 3 skin toxicity was observed in 16%. In addition, 35% developed acute grade 2a skin reactions. A trend was observed regarding grade 2-3 skin toxicities and administration of a boost (p=0.058). There was a significant association between the clinical target volume of the breast and grade 2-3 skin reactions in women who had breast-conserving surgery (p=0.016). Five patients (6%) developed grade 1 pneumonitis, unrelated to dosimetric or other baseline parameters. The toxicity profile after a median follow-up of 4 years was in accordance with published data. Recently, intensity-modulated techniques have been implemented at the study center, which may reduce radiotherapy toxicity in patients with large clinical target volume due to better dose homogeneity.

Correlation of PD-L1 expression with toxicities and response in oropharyngeal cancers treated with definitive chemoradiotherapy.

The programmed death receptor ligand 1 (PD-L1) is a cell-surface glycoprotein expressed in tumour cells (TCs) and is also upregulated in tumour infiltrating lymphocytes. The effect of PD-L1 expression on TCs and tumour-infiltrating lymphocytes (TILs) on acute radiation toxicity and response in oropharyngeal squamous cell carcinoma treated with concurrent chemoradiotherapy is less known. Squamous cell carcinoma of oropharynx with stage II-IVA (AJCC 8th) were recruited in this prospective observational study. Definitive radiation therapy (RT) of 70 Gray in 35 fractions at 2 Gray per fraction, 5 fractions a week in 2 phases was delivered with concurrent chemotherapy (cisplatin 40 mg/m2 weekly). Patients were assessed weekly for acute toxicities with Radiation Therapy Oncology Group criteria. Response assessment was done at 3 months post RT according to World Health Organization response assessment criteria. The programmed death receptor ligand 1 expression in TCs and TILs was correlated with acute toxicity and survival. Of 51 patients, 20 (39.2%) had PD-L1 expression in TCs and 18 (35.3%) in TILs. Patients with PD-L1 expression in TCs had fewer grade ≥ 3 oral mucositis (25% vs. 58%; p = 0.02) and grade ≥ 3 dysphagia (25% vs. 55%; p = 0.046). The programmed death receptor ligand 1-tumour infiltrating lymphocytes positives had lower ≥ 3 grade oral mucositis (22% vs. 58%; p = 0.02) and ≥ 3 grade dysphagia (17% vs. 58%; p = 0.007). Two-year overall and progression-free survival rate for the PD-L1-tumour-positive vs. PD-L1-tumour-negative group was not different (p > 0.5). Positive PD-L1 expression is associated with fewer acute radiation toxicities, and this could be used as a potential biomarker.

An Evaluation of Pain Response Between Single Fraction Radiotherapy Versus 10 Fractions RT in Metastatic Vertebral Bone Disease: A Quasi Experimental Study

The prognosis of bone metastasis is poor, with median survival measured in months, not years. Treatment remains an important issue to alleviate the complications and sufferings of the patients. This study was aimed to evaluate the pain response between single versus multiple fraction radiotherapy in metastatic vertebral bone disease. In this prospective quasi experimental study, the sample consisted of 60 patients of Oncology Dept., KYAMCH. Purposive sampling method was used. The respondents were divided into 2 arms, Arm A consisted of 30 patients, receiving 800 cGy single fraction RT, and Arm B consisted 30 patients who received 3000 cGy multiple fractions RT. The data were collected using a semi-structured questionnaire, which was constructed in line with the reviewed literature along with RECIST (Response Evaluation in Solid Tumor) criteria, VAS (Visual Analogue Scale) after 4 weeks of RT completion and Radiation Therapy Oncology Group (RTOG) criteria. Mean age of Arm A was 43.73 years, and Arm B was 46.8 years. Lung cancer was the leading cancer in both arms, 43.3% and 36.6% respectively. Adenocarcinoma was the commonest histopathological type of cancer found in both arms, 39.9% and 36.6% respectively. To determine associations, Chi-Square tests were done. For Arm A, 66.6% initially presented with severe pain, 23.31% with moderate and 10% with mild pain. In arm B 59.94%, 33.3% and 6.66% patients presented with severe, moderate and mild pain respectively. One month after completion of RT, pain significantly reduced in patients of both arms with a p value of < .001. No significant difference was observed between 8 Gy in single fraction versus 30 Gy in 10 fractions radiotherapy in the management of secondary bone tumour. It was found, both the radiation fractionation schedule for the management of secondary bone tumour are equally effective. More patients can be provided with the desired treatment with shorter period of time. It will certainly ease the economic burden on the patients as well as on the country.

The Relationship Between Late Morbidity and Dose-Volume Parameter of Rectum in Combined Intracavitary/Interstitial Cervix Cancer Brachytherapy: A Mono-Institutional Experience.

PurposeTo establish a dose volume–effect relationship for predicting late rectal complication (LRC) in locally advanced cervical cancer patients treated with external beam radiotherapy (EBRT) followed by combined intracavitary/interstitial brachytherapy (IC/IS-BT).Materials and MethodsA retrospective analysis was performed in 110 patients with locally advanced cervical cancer who underwent definitive radiotherapy combined with IC/IS-BT from July 2010 to September 2018. We report the 90% of the target volume receiving the minimum dose for high risk clinical target volume (HR-CTV D90) and intermediate risk clinical target volume (IR-CTV D90), and the minimum doses to the most exposed 0.1, 1, and 2 cm³ doses at the International Commission on Radiation Units and Measurements (DICRU) for organs at risk (OARs). The total dose of EBRT plus brachytherapy was transformed to the biologically equivalent dose in 2 Gy fractions (EQD2) with α/β value of 10 Gy for target, 3 Gy for organs at risk using the linear quadratic model. The morbidity was scored according to the Radiation Therapy Oncology Group (RTOG) criteria. The Probit model was used to establish a prediction model on rectum between the organs at risk for dose and LRC. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of dose volume parameters for LRC.ResultsThe median follow-up time was 72.3 months. The mean ( ± standard deviation) , and DICRU values of rectum were 64.72 ± 7.47 GyEQD2, 70.18 ± 5.92 GyEQD2, 79.32 ± 7.86 GyEQD2, and 67.22 ± 7.87 GyEQD2, respectively. The Probit model showed significant relationships between , and the probability of grade1–4, grade 2–4 rectal events at 1 year, and between and the probability of grade2–4 rectal events at 3 and 5 years. The dose values for 10% complication rates (ED10) of were 74.18 (70.42–76.71) GyEQD2, 67.80 (59.91, 71.08) GyEQD2, 66.37 (52.00, 70.27) GyEQD2 for grade 2–4 with rectal morbidity at 1, 3, and 5 years, respectively.ConclusionOur study proved that were considered as useful dosimetric parameters for predicting the risk of grade1–4 and grade2–4 LRC at 1-year, and might be an indicator for predicting grade2-4 LRC at 3/5years. The patients with rectal >66.37–74.18 GyEQD2 should be closely observed for grade2–4 LRC.

Comparison of preoperative and postoperative radiation therapy for extremity soft-tissue sarcoma: a randomized clinical trial

Background: The optimal sequencing of radiotherapy and surgery for the treatment of soft-tissue sarcoma (STS) is an ongoing source of controversy. In this study, the authors compared preoperative and postoperative radiotherapy in patients with extremity STS. Methods: Eighty patients with localized extremity STS were randomly assigned to either preoperative or postoperative radiotherapy group. Baseline characteristics of the patients were not significantly different between the two study groups. Primary outcome measures were pain, acute complications (wound dehiscence and infection), and late complications (limb edema, subcutaneous fibrosis, and joint stiffness). The severity of late complications was evaluated using the radiation therapy oncology group criteria. Secondary outcome measures were oncologic outcomes, including local recurrence and distant metastasis. Results: The mean pain level was not significantly different between the two groups (P=0.1). Infection was not seen in any of the patients. The rate of wound dehiscence and infection was not significantly different between the two groups (P=0.32 for both). Of the late complications, the rate of limb edema and subcutaneous fibrosis was similar in the two groups (P=0.16 and P=0.35, respectively). In contrast, the rate of joint stiffness was significantly more in the postoperative radiotherapy group (P&lt;0.001). The severity of all three late complications also was more in the postoperative radiotherapy group at 6 and 12 mo. There were no significant differences between the two groups regarding local recurrence and distant metastasis (P=0.99 and P=0.77, respectively). Conclusions: The authors suggest preoperative radiotherapy in patients with localized extremity STS because of its lower rate of and less severe complications, particularly joint stiffness. Level of Evidence: Level I.

Role of Palliative Chemoradiation in Locally Advanced Head and Neck Cancer

Background: Shorter palliative hypofractionated schedules when given concomitantly with chemotherapy, preferably cisplatin (radiosensitizer), enhance the response rate with acceptable toxicity, resulting in better compliance of the patients. Objectives: This case series retrospectively evaluated the role of concurrent chemotherapy, preferably cisplatin, with palliative radiation 30 Gy in 10 fractions in locally advanced head and neck cancers in terms of response rates, symptoms palliation, and acute toxicities. Materials and Methods: Twenty-six patients of histologically confirmed locally advanced head and neck cancers were selected and treated during the period January 2018 and December 2020. All patients (100%) completed the treatment with an average of two follow-ups. Results: The overall response rate of 73% was observed in patients treated, and interestingly, one patient had complete response. Moreover, 100% of the patients reported improvement in at least one symptom with severity reduction in pain. As defined by the Radiation Therapy Oncology Group (RTOG) criteria for toxicity assessment, Grade 2 mucositis in 61%, Grade 1 mucositis in 11%, Grade 1 skin reaction in 15% of the patients were observed. No grade III toxicity was reported. Conclusion: Concurrent chemotherapy acts as a radiosensitizer and provides a synergistic action when coupled with radiation resulting in more efficacious control of locoregional disease of locally advanced head and neck cancers with acceptable toxicities facilitating the compliance of patients.

Comparison of 2 dynamic conformal arc plans based on high-dose rate flattening filter free beams for peripheral lung cancer.

To compare 2 dynamic conformal arc plans based on the high dose rate flattening filter free (FFF) beams, and to evaluate the dosimetric differences. A total of 20 patients with early peripheral non-small cell lung cancer were selected, and 2 dynamic conformal arc plans were designed in the Eclipse 10.0 treatment planning system (TPS). One of them was based on tumor-center (T-DCA), and the other was based on iso-center (Iso-DCA). Both plans were created by using the Truebeam linear accelerator, based on 6 MV FFF photons with a dose rate at 1 400 monitor unit (MU)/min. All patients received the prescribed dose of 4 800 cGy in 4 fractions (1 200 cGy/fraction). Target coverage and organ at risk limits were planned and designed according to the Radiation Therapy Oncology Group (RTOG) Criteria, and were compared between the T-DCA and the Iso-DCA plans. There was no significant difference in the target coverage between the T-DCA and Iso-DCA plans (P>0.05). Conformal index and homogeneity index had no significant differences (both P>0.05), but the percentage of the maximum dose in any direction 2 cm away from the planned target area (D2 cm) and the ratio of the volume wrapped by the isodose line of 50% prescription dose to the volume of the planned target area (R50%) showed significant differences (both P<0.05). The MU of the Iso-DCA plan was increased by 21% compared with that of the T-DCA plan. Except the maximum dose of spinal cord and esophagus, there was no significant difference in the other dosimetric parameters of the organs at risk between the T-DCA and the Iso-DCA plans (all P>0.05). The dose fall-off of Iso-DCA plan is better than T-DCA plan, but the T-DCA plan is consistently superior in sparing dose to spinal cord and esophagus, and the T-DCA plan has fewer MU.

Aloe vera for Prevention of Acute Radiation Proctitis in Colorectal Cancer a Preliminary Randomized, Placebo-Controlled Clinical Trial.

To examine the preventive effects of Aloe vera in colorectal cancer patients undergoing radiotherapy. Twenty colorectal cancer patients, who received radiation, were randomized to receive Aloe vera 3% or placebo ointment, 1g twice daily for 6weeks. At weekly visits, acute radiation proctitis (ARP) was evaluated by Radiation Therapy Oncology Group and clinical presentation criteria as the primary endpoint. We also evaluated secondary endpoints of quality of life, psychosocial status, by applying Hospital Anxiety-Depression (HAD) Scale and laboratory measures of quantitative measurement of C-reactive protein (CRP) as a marker for systemic inflammation. There was a significant improvement in the symptom index (before treatment vs. after treatment with Aloe vera) for diarrhea (p=0.029, median score: 0.5 vs. 0.001). The overall primary and secondary outcomes favored Aloe group, while the measures of toxicity did not achieve a statistical significant difference. The lifestyle score improved significantly with A. vera (p=004), and they also had a lower depression score in HAD scale (p=0.008). Furthermore, quantitative CRP decreased significantly during the course of treatment with Aloe vera. The use of topical formulation of Aloe vera 3% diminishes the severity of ARP in colorectal cancer patients.

Durability of the parotid-sparing effect of intensity-modulated radiotherapy (IMRT) in early stage nasopharyngeal carcinoma: A 15-year follow-up of a randomized prospective study of IMRT versus two-dimensional radiotherapy.

The durability of improved xerostomia with intensity-modulated radiotherapy (IMRT) in patients with early stage nasopharyngeal carcinoma (NPC) is uncertain. We conducted a long-term prospective assessment of participants treated with IMRT or two-dimensional radiotherapy (2DRT) in a prior randomized study. Parent study participants (IMRT, n = 28; 2DRT, n = 28) who were free of second malignancy or recurrence were eligible. Long-term radiotherapy-related toxicities were graded according to the Radiation Therapy Oncology Group (RTOG) criteria. Long-term patient-reported outcomes were assessed by the six-item xerostomia (XQ) and two European Organisation for Research and Treatment of Cancer (EORTC) questionnaires (QLQ-C30, QLQ-H&N35). Overall survival (OS), locoregional relapse-free survival (LRFS), distant relapse-free survival (DRFS), and the rate of symptomatic late complications (SLCs) were estimated for the entire cohort (n = 56). Totally, 21 (IMRT, n = 10; 2DRT, n = 11) patients gave consent and were assessed for an overall median follow-up of 15.5 years. There was significantly less RTOG ≥grade 2 xerostomia with IMRT versus 2DRT (20% vs. 90%; p = 0.001), but no significant difference in XQ scores. Patients in the IMRT arm reported lower mean scores for the "dry mouth" domain of EORTC QLQ-H&N35 (p = 0.02) and showed trends toward better 15-year OS (81.5% vs. 53.8%, p = 0.06), LRFS (70.6% vs. 53.8%, p = 0.38), and DRFS (81.5% vs. 53.8%, p = 0.07). SLCs were more frequent in the 2DRT arm. The parotid-sparing effect of IMRT in NPC treatment is durable, with significantly less physician- and patient-scored xerostomia at 15 years. IMRT results in better long-term survival and fewer SLCs.

Changes in Pulmonary Function and Development of Clinical Radiation Pneumonitis in Breast Cancer Patients following Post Mastectomy Radiation Therapy

Background: Lung is the main organ at risk for radiation induced injury while treating breast cancers with Post Mastectomy Radiotherapy (PMRT). Restrictive lung changes are usually seen in spirometry which tends to normalize by 1 year. Central Lung Distance (CLD) is shown to correlate well with the percentage of ipsilateral lung volume irradiated. Aims and Objectives: Spirometric changes following Radiation Therapy (RT) to chest wall in breast cancer patients using conventional fractionation and its correlation with acute radiation pneumonitis. Materials and Methodology: Thirty Breast cancer patients who received RT to chest wall +/- supraclavicular fossa and axilla, following Modified Radical Mastectomy (MRM) and neoadjuvant or adjuvant chemotherapy using tangential beams with Co60 teletherapy to a dose of 50 Gray in conventional fractionation were included and followed up till 6 months post RT. Baseline chest X-ray and spirometry done pre-RT were compared with those taken at 1, 3 and 6 months after completion of RT. Patients were evaluated at each visit for signs and symptoms of radiation pneumonitis, when present were graded as per Radiation Therapy Oncology Group (RTOG) criteria. Results: There was a significant fall in Forced Vital Capacity (FVC) by the end of 3 months (p value &lt;0.01) which improved by 6 months without any active intervention in 95% of the patients. Mean baseline FVC was 83% which decreased to 70% by the end of 3 months and 79% at 6 months. Forced Expiratory Volume in first second (FEV1) and FEV1/FVC did not show any significant change compared to baseline. Spirometric changes correlated with reversible restrictive lung changes. One out of 30 patients developed symptomatic acute radiation pneumonitis (5%) of grade 3 severity who had moderate restrictive lung disease. Conclusion: Significant decrease in FVC of the lungs is present following PMRT in carcinoma of breast patients in the initial 3 months which tends to normalize by 6 months. 5% of the patients develop symptomatic acute lung toxicity which can be further reduced by minimizing the irradiated lung volume.

"Christie Regimen" palliative radiotherapy in advanced head-and-neck cancer: A single-center experience.

Relevance of aggressive treatment in advanced head neck squamous cell cancers(HNSCC) is debatable in view of expected poor outcome. Long treatment duration only adds up to the cost of treatment without any improvements in outcomes. To assess the outcomes of hypofractionated "Christie" palliative radiotherapy regimen in advanced HNSCC. Patients of advanced HNSCC registered from June 2015 to June 2019 were treated by parallel pair field technique on Cobalt60 machine (Theatron 780E) to total dose of 50 Gray/16 fractions over 3.2 weeks. Toxicity was scored using Radiation Therapy Oncology Group (RTOG) criteria and response was evaluated as per WHO criteria. Records of 110 patients of HNSCC with mean age of 56.19 years were analysed. Evaluation at 4-8 weeks after radiotherapy resulted in a complete response (CR) in 19.1%, partial response (PR) in 32.7%, stable disease (SD) in 29.1% and progressive disease (PD) in 3.6%, while 15.5% patients did not report for post treatment evaluation. Median progression free survival was 9.52 months (95% CI 5.9 - 13.1 months). The median overall survival was 12.7 ± 2.2 months (95% CI 8.2 - 17.2). Median time to progression after completion of radiotherapy was 84 days. Grade IV dermatitis and mucositis was encountered in 2.7% and 1.8% cases respectively, requiring hospitalization. Christie regimen for advanced HNSCC is a clinically viable option with acceptable outcomes in a resource constrained setting.

A Prospective Trial of Radiation Therapy Efficacy and Toxicity for Localized Mucosa-associated Lymphoid Tissue (MALT) Lymphoma

Radiation therapy is an effective therapy for extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). We report the long-term results of a prospective trial conducted to determine the efficacy and toxicity of radiation therapy (RT) alone in treating MALT lymphoma. Patients with stage I or II MALT lymphoma or with stage IV disease due to bilateral parotid, ocular/ocular adnexal involvement, or from multiple sites within Waldeyer’s ring were eligible. Radiation treatment consisted of involved field RT starting with 39.6 Gray (Gy) later amended down to 24 Gy. Relapse-free survival was the primary endpoint. Clinical, radiographic and/or endoscopic response was assessed beginning 3 months after treatment. Acute and late toxicities were evaluated per Radiation Therapy Oncology Group (RTOG) criteria v3.0. Kaplan-Meier analysis was used to estimate time to progression (TTP), relapse free survival (PFS), progression free survival (PFS) and overall survival (OS) defined from the time of study entry. Preplanned subgroup analyses of outcome were performed based on site of involvement. From 2000-2012, 75 patients were accrued; 73 received protocol-specified RT. Median follow-up was 9.8 years for the 62 alive patients. Sixty-nine patients (95%) had a complete response at time of first restaging and the remaining 4 achieved CR with additional observation. Eleven patients (15%) had disease relapse, 9 of which were at sites outside of the radiation treatment field with median time to progression of 37.5 months. The two local relapses were in the stomach, 13.7 and 84.9 months after completion of RT. Median PFS was 17.5 years and median RFS and OS were not reached. 10-year relapse-free rate was 83% (95% CI 74-93%). 10-year PFS rate was 71% (95% CI 60-84%). 10-year OS rate was 86% (95% CI 77-96%). TTP, PFS, and OS did not differ by site of involvement (P = 0.18, 0.43, 0.50). All relapses were successfully salvaged most commonly with rituximab alone (n = 3), RT (n = 3), or chemotherapy (n = 2). One patient developed metastatic gastric adenocarcinoma and was found to also have recurrent MALT on biopsy. Otherwise, all relapsed patients were alive without evidence of disease at last follow up, and no patient died due to MALT lymphoma. Sixty-seven patients (92%) experienced acute toxicity during radiation, all of which were grade 1 and 2 with only 1 grade 3 toxicity of the eye (retinal detachment). Twenty-two patients (30%) experienced late toxicity, with only one Grade 3 toxicity (eye) in the same patient with G3 acute eye toxicity. No patients had subsequent disease transformation to aggressive lymphoma. This prospective study confirms that RT for MALT lymphoma provides excellent long-term relapse free survival with acceptable rates of toxicity. Current efforts are focused on RT de-escalation in an effort to further reduce toxicity risk.

EQD2 Analyses of Vaginal Complications in Exclusive Brachytherapy for Postoperative Endometrial Carcinoma.

Simple SummaryVaginal complications in exclusive vaginal-cuff brachytherapy (EVCBT) have not been analyzed in terms of the dose received by a vaginal volume of 2 cm3. The aim of this work was to analyze the vaginal dose and complications in EVCBT. In the present analysis, we found that all the patients receiving < 68Gy equivalent dose 2Gy/day at 2 cm3 of the most exposed area to the dose of the vagina only developed G0–G1 and 1G2 without vaginal stenosis complications and without relapses. This dose limit could eliminate G2 vaginal stenosis and is the hypothesis of a new analysis in our center.Background: To evaluate whether EQD2(α/β = 3Gy) at 2 cm3 of the most exposed area of the vagina is related to late vaginal toxicity in postoperative endometrial cancer (PEC) patients (p) treated with exclusive brachytherapy (BT). Methods: From 2014 to 2017, 43p were included in this study. BT was administered: 3-fractions of 6Gy in 37p and 2-fractions of 7.5Gy in 6p. The dose was prescribed at a depth of 5 mm from the applicator surface with dose-point optimization based on distance. The active treatment length was 2.5 cm. CTV-D90 and the dose to the most exposed 2 cm3 of the vagina was calculated for each patient. Late toxicity of the bladder and rectum was assessed using Radiation Therapy Oncology Group (RTOG) criteria, and vaginal toxicity by objective Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA) (LENT-SOMA) criteria. Statistics: frequency tables, mean, median, range, standard deviation, and box plot. Results: The median follow-up was 51 months (12–68). 20 p (46.5%) and 2 p (4.7%) developed G1 and G2 vaginal complications, respectively. Only 1/2 p-G2 receiving EQD2(α/β = 3Gy) at 2 cm3 >68Gy presented vaginal shortening and 18/20 p-G1 received doses < 68Gy. Conclusions: PECp receiving exclusive brachytherapy with doses < 68Gy EQD2(α/β = 3Gy) at 2 cm2 of the vagina presented only G0–G1 vaginal toxicity, except for one with bleeding telangiectasias. Larger prospective studies are necessary to confirm the present results.

A combined protocol with piroxicam, chemotherapy, and whole pelvic irradiation with simultaneous boost volumetric modulated arc radiotherapy for muscle-invasive canine urinary transitional cell carcinoma: First clinical experience.

The aims of this pilot study were to evaluate the feasibility and efficacy of high-dose hypofractionated volumetric modulated arc radiotherapy (VMAT) applied to whole pelvic region radiotherapy (WPRT) with multilevel simultaneous integrated boost (MLSIB) combined with piroxicam and chemotherapy for the treatment of canine transitional cell carcinoma (TCC) of the lower urinary tract with muscle invasion TCC. Twelve dogs were enrolled, according to stage, in two groups: group 1, TCC confined to the urinary tract; group 2, TCC with metastasis. The planning target volume dose was tailored from 36 to 42 Gy in 6 fractions. All dogs were prescribed piroxicam and radiosensitizing carboplatin, and six received chemotherapy after radiotherapy. Serial follow-ups with computed tomography and magnetic resonance imaging were performed. Disease control and toxicity effects were evaluated according to the Response Evaluation Criteria in Solid Tumors and Veterinary Radiation Therapy Oncology Group criteria. The treatment was well tolerated, and no high-grade side effects were reported. The median overall survival times for groups 1 and 2 were 1,230 and 150 days, respectively. A considerable percentage of patients in group1 (50%) were still alive at the time of writing this paper, and a longer follow-up could enable a more accurate survival analysis. This preliminary analysis shows that VMAT applied to the WPRT with MLSIB is an effective and safe option for dogs with lower urinary TCC, although the presence of metastases worsens the prognosis.

Ten-Year Results From a Phase II Study on Image Guided, Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost in High-Risk Prostate Cancer

PurposeThere is no consensus on how to treat high-risk prostate cancer, and long-term results from hypofractionated radiation therapy are lacking. We report 10-year results after image guided, intensity modulated radiation therapy with hypofractionated simultaneous integrated boost and elective pelvic field. Methods and MaterialsBetween 2007 and 2009, 97 consecutive patients with high-risk prostate cancer were included, treated with 2.7 to 2.0 Gy × 25 Gy to the prostate, seminal vesicles, and elective pelvic field. Toxicity was scored according to Radiation Therapy Oncology Group criteria and biochemical disease-free survival (BFS) defined by the Phoenix definition. Patients were subsequently divided into 3 groups: high risk (HR; n = 32), very high risk (VHR; n = 50), and N+/s–prostate-specific antigen (PSA) ≥100 (n = 15). Differences in outcomes were examined using Kaplan-Meier analyses. ResultsBFS in the patients at HR and VHR was 64%, metastasis-free survival 80%, prostate cancer-specific survival 90%, and overall survival (OS) 72%. VHR versus HR subgroups demonstrated significantly different BFS, 54% versus 79% (P = .01). Metastasis-free survival and prostate cancer-specific survival in the VHR group versus HR group were 76% versus 87% (P = .108) and 74% versus 100% (P = .157). Patients reaching nadir PSA <0.1 (n = 80) had significantly better outcomes than the rest (n = 17), with BFS 70% versus 7% (P < .001). Acute grade 2 gastrointestinal tract (GI) and genitourinary tract (GU) toxicity occurred in 27% and 40%, grade 3 GI and GU toxicity in 1% and 3%. Late GI and GU grade 2 toxicity occurred in 1% and 8%. ConclusionsHigh-risk prostate cancer patients obtained favorable 10-year outcomes with low toxicity. There were significantly better results in the HR versus the VHR group, both better than the N+/PSA ≥100 group. A nadir PSA value < 0.1 predicted good prognosis.

Toxicity of Immune Checkpoint Inhibitors and Radiotherapy: A Systematic Review and Meta-Analysis of 35 Studies and 7,000 Patients

Combination radiation therapy (RT) and immune checkpoint inhibitor (ICI) therapy is an evolving treatment paradigm. There may be a survival benefit for concurrent over non-concurrent administration of ICIs, but the toxicities of the approaches have not been characterized. We hypothesize that there is no measurable difference in toxicity between ICI alone vs ICI + RT, delivered either concurrent or non-concurrently. The primary outcome measure is grade 3-4 toxicities by the Common Terminology Criteria for Adverse Events (CTCAE) or Radiation Therapy Oncology Group (RTOG) criteria. Using a PICOS/PRISMA/MOOSE selection protocol, studies were identified from PubMed and the 2019 National Comprehensive Cancer Network guidelines. Inclusion criteria were: (1) population: patients of any age with malignancy; (2) intervention: treatment with ICI, with or without RT; (3) control: no control group, ICI alone arm, or RT alone arm; (4) outcomes: CTCAE/RTOG toxicities; (5) setting: for ICI alone, single or multi-arm prospective studies; for ICI+RT, retro or prospective studies. Weighted random effects meta-analyses were conducted for toxicities using the Dersimonian and Laird method. A total of 388 studies met initial criteria, 98 were screened, and 35 studies (N), with 7016 patients (n), were included. For ICI + RT, median radiation dose was 20 Gy in 1 fraction, grade 3-4 radionecrosis was observed in 2 patients, and there were no grade 5 toxicities. The rate of grade 3-4 toxicities for ICI alone was 19.4% (95% CI 15.3-23.9%, I2 95%) vs ICI + RT 22.1% (95% CI 5.2-44.9%, I2 90%), as shown in Table 1. Addition of RT to ICI therapy (concurrently or non-concurrently) does not appear to increase rate of grade 3-4 toxicity, which is seen in about 1 of 5 patients. Future study of RT alone will elucidate the RT-related toxicities experienced by ICI + RT patients, and upcoming large-scale randomized clinical trials of ICI + RT will provide stronger evidence for ICI + RT safety and efficacy.Abstract 3510; Table 1Grade 3-4 toxicities of ICI alone vs ICI + RTTherapyStudies (N)Disease sitePro vs retrospectivePatients (n)Grade 3-4 toxicity (95% confidence interval)I2ICI alone29head/neck, gastric, melanoma, mesothelioma, non-small cell lung, kidney, prostate, and urothelialAll prospective682219.4% (15.3-23.9%)95%ICI + RT (not mutually exclusive)6brain metastases, pooled metastases to all organs3 prospective 3 retrospective19422.1% (5.2-44.9%)90%Concurrent arms5 (6 arms)9023.9% (3.5-54.3%)89%Non-concurrent arms2 (3 arms)826.6% (0.0-29.3%)85%Mixed arm1 (1 arm)2268.2% (47.0-86.3%) Open table in a new tab