Independently validated sex-specific nomograms for predicting survival in patients with newly diagnosed glioblastoma: NRG Oncology RTOG 0525 and 0825.

BACKGROUND/PURPOSE: Glioblastoma (GBM) is the most common primary malignant brain tumor. Sex has been shown to be an important prognostic factor for GBM. The purpose of this study was to develop and independently validate sex-specific nomograms for estimation of individualized GBM survival probabilities using data from 2 independent NRG Oncology clinical trials. METHODS: This analysis included information on 752 (NRG/RTOG 0525) and 599 (NRG/RTOG 0825) patients with newly diagnosed GBM. The Cox proportional hazard models by sex were developed using NRG/RTOG 0525 and significant variables were identified using a backward selection procedure. The final selected models by sex were then independently validated using NRG/RTOG 0825. RESULTS: Final nomograms were built by sex. Age at diagnosis, KPS, MGMT promoter methylation and location of tumor were common significant predictors of survival for both sexes. For both sexes, tumors in the frontal lobes had significantly better survival than tumors of multiple sites. Extent of resection, and use of corticosteroids were significant predictors of survival for males. CONCLUSIONS: A sex specific nomogram that assesses individualized survival probabilities (6-, 12- and 24-months) for patients with GBM could be more useful than estimation of overall survival as there are factors that differ between males and females. A user friendly online application can be found here- https://npatilshinyappcalculator.shinyapps.io/SexDifferencesInGBM/ .

Role of radiation in extensive stage small cell lung cancer: a National Cancer Database registry analysis.

The role of prophylactic cranial irradiation (PCI) and thoracic radiation therapy (TRT) in extensive-stage small cell lung cancer remains controversial. The authors examined the National Cancer Database and identified patients with extensive-stage small cell lung cancer with no brain metastasis. Patients were excluded if they died 30 days from diagnosis, did not receive polychemotherapy, had other palliative radiation or had missing information. A propensity score-matched analysis was also performed. A total of 21,019 patients were identified. The majority of patients did not receive radiation (69%), whereas 10% received PCI and 21% received TRT. The addition of PCI and TRT improved median survival and survival at 1 and 2 years (p ≤ 0.05). The propensity score-matched analysis confirmed the same overall survival benefit with both PCI and TRT. This registry-based analysis of >1500 accredited cancer programs shows that PCI and TRT are not commonly utilized for extensive-stage small cell lung cancer patients who are treated with multiagent chemotherapy. The addition of PCI and TRT significantly improves overall survival in this otherwise poor prognostic group. Further research is needed to confirm the role of PCI and TRT, especially in the era of improved systemic therapy.

Lay abstract The role of radiation therapy in patients with metastatic small cell lung cancer remains controversial. The authors examined the National Cancer Database and identified patients with metastatic small cell lung cancer without brain metastasis. Patients were excluded if they died 30 days from diagnosis, did not receive multiagent chemotherapy, had other palliative radiation or had missing information regarding treatment. A total of 21,019 patients were identified. The majority of patients did not receive radiation (69%), whereas 10% received radiation to the brain and 21% received radiation to their lungs. The addition of brain and lung radiation therapy improved median survival and survival at 1 and 2 years. The addition of prophylactic cranial irradiation and thoracic radiation therapy improves survival in extensive-stage small cell lung cancer. Future research is needed to evaluate the role of radiation in the era of chemoimmunotherapy.

Higher Doses of Neoadjuvant Radiation for Esophageal Cancer Do Not Affect the Pathologic Complete Response Rate or Survival: A Propensity-Matched Analysis.

BACKGROUND: Traditional neoadjuvant therapy for esophageal cancer has used chemoradiation doses greater than 45 Gy. This study aimed to examine the dose of preoperative radiation in relation to the pathologic complete response (pCR) rate and overall survival (OS) for patients with resectable esophageal cancer. METHODS: The National Cancer Database was queried for all patients with esophageal or gastroesophageal junction cancer who received neoadjuvant chemoradiation (CRT) followed by esophagectomy between 2006 and 2015. The radiation doses were divided into four ranges based on Grays (Gy) received: less than 39.6 Gy, 39.60-44.99 Gy, 45-49.99 Gy, and 50 Gy or more. RESULTS: The inclusion criteria were met by 10,293 patients. All patients received neoadjuvant CRT, with 689 patients (6.7%) receiving less than 39.6 Gy, 973 patients (9.5%) receiving 39.6-44.9 Gy, 3837 patients (37.3%) receiving 45-49.9 Gy, and 4794 patients (46.6%) receiving 50 Gy or more. The overall pCR rate was 17.2% (1769/10,293) and was significantly lower for those who received less than 39.6 Gy of radiation than for those who received 39.6 Gy or more (13.9% [96/689] vs. 17.4% [1673/9604]; p = 0.017). The median OS of 37.2 months was significantly better for those who received 39.6 Gy or more than for those who received less than 39.6 Gy (38 vs. 29.6 months (p < 0.0001). The pCR and OS did not differ between the three higher radiation doses (39.6-44.9 vs. 45-49.9 Gy vs. ≥ 50 Gy; pCR [p = 0.1] vs. OS [p = 0.097]). The patients who received 39.6-44.9 Gy were propensity matched with those who received 45 Gy or more of radiation. There remained no difference in pCR (p = 0.375) or OS (p = 0.957). CONCLUSIONS: In the United States, the heterogeneity in neoadjuvant CRT dosing is significant, with 84% of patients receiving more than 45 Gy. The benefit of neoadjuvant CRT in terms of pCR and overall  survival is seen with doses of 39.6 Gy or more, but not with doses higher than 45 Gy.

Post-radiotherapy PET/CT for predicting treatment outcomes in head and neck cancer after postoperative radiotherapy.

PURPOSE: The purpose of this study was to retrospectively review the role of post-treatment (post-tx) FDG-PET/CT scans in patients receiving postoperative intensity-modulated radiotherapy (IMRT) for head and neck squamous cell carcinomas (HNSCC). MATERIALS AND METHODS: Eighty-two patients with HNSCC treated with surgery and postoperative IMRT with or without chemotherapy from October 15, 2008 to December 31, 2014 that had post-tx PET/CT within 6 months of completing IMRT were included. PET/CT was considered positive based on multi-disciplinary review integrating clinical information. Survival analysis was performed using the Kaplan-Meier method. Categorical and continuous predictors of positive post-tx PET/CT were evaluated using Fisher's exact test and logistic regression, respectively. Predictors for survival outcomes were evaluated with log-rank testing. A p ≤ 0.05 was considered statistically significant. RESULTS: Median follow-up was 3.88 years. For all patients, 3-year overall survival (OS) and recurrence-free survival (RFS) were 71.8% and 61.3%, respectively. Patients with positive post-tx PET/CT had worse OS compared to those with negative post-tx PET/CT (log rank p < 0.001). For patients with positive post-tx PET/CT, 3-year OS was 11.2% compared to 89.9% for patients with negative post-tx PET/CT. The positive predictive value (PPV) of PET/CT was 100% for local recurrence (LR), regional recurrence (RR) and distant metastasis (DM). The negative predictive values (NPV) for LR, RR and DM were 89.0%, 89.2%, and 85.9%, respectively. Perineural invasion (p = 0.009), p16 status (p = 0.009), non-oropharyngeal primary site (p = 0.002), and the use of chemotherapy (p = 0.01) were independent predictors of positive PET/CT. CONCLUSIONS: Post-tx PET/CT after postoperative radiation is prognostic for survival outcomes. The PPV of post-tx PET for recurrence was excellent, allowing for early detection of recurrent disease. Post-tx PET/CT should be considered after postoperative radiation.

Comparison of multiparametric MRI-based and transrectal ultrasound-based preplans with intraoperative ultrasound-based planning for low dose rate interstitial prostate seed implantation.

PURPOSE: Transrectal ultrasound images are routinely acquired for low dose rate (LDR) prostate brachytherapy dosimetric preplanning (pTRUS), although diagnostic multiparametric magnetic resonance imaging (mpMRI) may serve this purpose as well. We compared the predictive abilities of TRUS vs MRI relative to intraoperative TRUS (iTRUS) to assess the role of mpMRI in brachytherapy preplanning. MATERIALS AND METHODS: Retrospective analysis was performed on 32 patients who underwent iTRUS-guided prostate LDR brachytherapy as either mono- or combination therapy. 56.3% had pTRUS-only volume studies and 43.7% had both 3T-mpMRI and pTRUS preplanning. MRI was used for preplanning and its image fusion with iTRUS was also used for intraoperative guidance of seed placement. Differences in gland volume, seed number, and activity and procedure time were examined, as well as the identification of lesions suspicious for tumor foci. Pearson correlation coefficient and Fisher's Z test were used to estimate associations between continuous measures. RESULTS: There was good correlation of planning volumes between iTRUS and either pTRUS or MRI (r = 0.89, r = 0.77), not impacted by the addition of hormonal therapy (P = 0.65, P = 0.33). Both consistently predicted intraoperative seed number (r = 0.87, r = 0.86). MRI/TRUS fusion did not significantly increase surgical or anesthesia time (P = 0.10, P = 0.46). mpMRI revealed suspicious focal lesions in 11 of 14 cases not visible on pTRUS, that when correlated with histopathology, were incorporated into the plan. CONCLUSIONS: Relative to pTRUS, MRI yielded reliable preplanning measures, supporting the role of MRI-only LDR treatment planning. mpMRI carries numerous diagnostic, staging and preplanning advantages that facilitate better patient selection and delivery of novel dose escalation and targeted therapy, with no additional surgical or anesthesia time. Prospective studies assessing its impact on treatment planning and delivery can serve to establish mpMRI as the standard of care in LDR prostate brachytherapy planning.

Assessment of beam-matched linacs quality/accuracy for interchanging SBRT or SRT patient using VMAT without replanning.

PURPOSE: Dosimetric accuracy is critical when switching a patient treated with stereotactic body radiation therapy (SBRT) or stereotactic fractionated radiotherapy (SRT) among beam-matched linacs. In this study, the dose delivery accuracy of volumetric modulated arc therapy (VMAT) plans for SBRT/SRT patients were evaluated on three beam-matched linacs. METHOD: Beam data measurements such as percentage depth dose (PDD10 ), beam profiles, output factors, and multi-leaf collimator (MLC) leaf transmission factor for 6 MV photon beam were performed on three beam-matched linacs. The Edge™ diode detector was used for measurements of beams of field size less than 5 × 5 cm2 . Ten lung and 15 brain plans were generated using VMAT with the same beam model. Modulation complexity score of the VMAT plan (MCSv) was used as a plan complexity indicator. Doses were measured using ArcCHECK™ and GafChromic™ EBT3 films. The measurements were compared with calculated doses through absolute dose gamma comparison using 3%/2 mm and 2%/2 mm criteria. Correlation between difference in passing rates among beam-matched linacs and MCSv was evaluated using the Pearson coefficient. Point doses were measured with the A1SL micro ion chamber. RESULTS: Difference in beam outputs, beam profiles, and MLC leaf transmission factors of beam-matched linacs were all within ±1%, except the difference in output factor for 1 × 1 cm2 field between linac 1 and 3 (1.3%). For all 25 cases, passing rates of measured doses on three linacs were all higher than 90% when using 2%/2 mm gamma criteria. The average difference in point dose measurements among three beam-matched linacs was 0.1 ± 0.2% (P > 0.05, one-way ANOVA). CONCLUSION: Minimal differences in beam parameters, point doses, and passing rates among three linacs proved the viability of swapping SBRT/SRT using VMAT among beam-matched linacs. The effect of plan complexity on passing rate difference among beam-matched linacs is not statistically significant.

Postoperative hypofractionated stereotactic brain radiation (HSRT) for resected brain metastases: improved local control with higher BED10.

INTRODUCTION: HSRT directed to large surgical beds in patients with resected brain metastases improves local control while sparing patients the toxicity associated with whole brain radiation. We review our institutional series to determine factors predictive of local failure. METHODS: In a total of 39 consecutive patients with brain metastases treated from August 2011 to August 2016, 43 surgical beds were treated with HSRT in three or five fractions. All treatments were completed on a robotic radiosurgery platform using the 6D Skull tracking system. Volumetric MRIs from before and after surgery were used for radiation planning. A 2-mm PTV margin was used around the contoured surgical bed and resection margins; these were reviewed by the radiation oncologist and neurosurgeon. Lower total doses were prescribed based on proximity to critical structures or if prior radiation treatments were given. Local control in this study is defined as no volumetric MRI evidence of recurrence of tumor within the high dose radiation volume. Statistics were calculated using JMP Pro v13. RESULTS: Of the 43 surgical beds analyzed, 23 were from NSCLC, 5 were from breast, 4 from melanoma, 5 from esophagus, and 1 each from SCLC, sarcoma, colon, renal, rectal, and unknown primary. Ten were treated with three fractions with median dose 24 Gy and 33 were treated with five fractions with median dose 27.5 Gy using an every other day fractionation. There were no reported grade 3 or higher toxicities. Median follow up was 212 days after completion of radiation. 10 (23%) surgical beds developed local failure with a median time to failure of 148 days. All but three patients developed new brain metastases outside of the treated field and were treated with stereotactic radiosurgery, whole brain radiation and/or chemotherapy. Five patients (13%) developed leptomeningeal disease. With a median follow up of 226 days, 30 Gy/5 fx was associated with the best local control (93%) with only 1 local failure. A lower total dose in five fractions (ie 27.5 or 25 Gy) had a local control rate of 70%. For three fraction SBRT, local control was 100% using a dose of 27 Gy in three fractions (follow up was > 600 days) and 71% if 24 Gy in three fractions was used. A higher total biologically equivalent dose (BED10) was statistically significant for improved local control (p = 0.04) with a threshold BED10 ≥ 48 associated with better local control. CONCLUSIONS: HSRT after surgical resection for brain metastasis is well tolerated and has improved local control with BED10 ≥ 48 (30 Gy/5 fx and 27 Gy/3 fx). Additional study is warranted.

Comparative analysis for renal stereotactic body radiotherapy using Cyberknife, VMAT and proton therapy based treatment planning.

PURPOSE: We conducted this dosimetric analysis to evaluate the feasibility of a multi-center stereotactic body radiation therapy (SBRT) trial for renal cell carcinoma (RCC) using different SBRT platforms. MATERIALS/METHODS: The computed tomography (CT) simulation images of 10 patients with unilateral RCC previously treated on a Phase 1 trial at Institution 1 were anonymized and shared with Institution 2 after IRB approval. Treatment planning was generated through five different platforms aiming a total dose of 48 Gy in three fractions. These platforms included: Cyberknife and volumetric modulated arc therapy (VMAT) at institution 1, and Cyberknife, VMAT, and pencil beam scanning (PBS) Proton Therapy at institution 2. Dose constraints were based on the Phase 1 approved trial. RESULTS: Compared to Cyberknife, VMAT and PBS plans provided overall an equivalent or superior coverage to the target volume, while limiting dose to the remaining kidney, contralateral kidney, liver, spinal cord, and bowel. CONCLUSION: This dosimetric study supports the feasibility of a multi-center trial for renal SBRT using PBS, VMAT and Cyberknife.

Metabolic tumor volume predicts overall survival and local control in patients with stage III non-small cell lung cancer treated in ACRIN 6668/RTOG 0235.

PURPOSE: To determine whether higher pre-treatment metabolic tumor volume (tMTV-pre) is associated with worse overall survival (OS) in patients with inoperable NSCLC treated with definitive chemoradiation (CRT). METHODS: This is a secondary analysis of the American College of Radiology Imaging Network (ACRIN) 6668/Radiation Therapy Oncology Group 0235 trial. Pre-treatment PET scans were performed on ACRIN-qualified scanners. Computer-aided MTV measurement was performed using RT_Image. Kaplan-Meier curves and Cox proportional hazards regression models were used to assess the association between tMTV and OS. RESULTS: Of the 250 patients enrolled on the study, 230 were evaluable for tMTV-pre. Patients with MTV-pre >32 mL (median value) vs. ≤32 mL had worse median OS (14.8 vs. 29.7 months, p < 0.001). As a continuous variable, higher tMTV-pre (per 10-mL increase) remained associated with worse OS (HR = 1.03, p < 0.001) after controlling for other variables. A significant interaction between radiation dose and tMTV-pre occurred for OS (p = 0.002), demonstrating that the negative prognostic impact of tMTV-pre decreased as radiotherapy dose increased. Among patients with tMTV-pre ≤32 mL, there was no difference in survival according to radiotherapy dose delivered (p = 0.694). However, median OS was inferior in patients with tMTV-pre >32 mL who received ≤60 Gy compared with those who received 61-69 Gy or ≥70 Gy (p = 0.001). CONCLUSIONS: Higher tMTV-pre is associated with significantly worse OS in inoperable stage III NSCLC treated with definitive CRT. Our findings suggest that for patients with large tMTV-pre, achieving a therapeutic radiation dose may help maximize OS. Prospective studies are needed to confirm this finding.

Optimal FDG PET/CT volumetric parameters for risk stratification in patients with locally advanced non-small cell lung cancer: results from the ACRIN 6668/RTOG 0235 trial.

PURPOSE: In recent years, multiple studies have demonstrated the value of volumetric FDG-PET/CT parameters as independent prognostic factors in patients with non-small cell lung cancer (NSCLC). We aimed to determine the optimal cut-off points of pretreatment volumetric FDG-PET/CT parameters in predicting overall survival (OS) in patients with locally advanced NSCLC and to recommend imaging biomarkers appropriate for routine clinical applications. METHODS: Patients with inoperable stage IIB/III NSCLC enrolled in ACRIN 6668/RTOG 0235 were included. Pretreatment FDG-PET scans were quantified using semiautomatic adaptive contrast-oriented thresholding and local-background partial-volume-effect-correction algorithms. For each patient, the following indices were measured: metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVmax, SUVmean, partial-volume-corrected TLG (pvcTLG), and pvcSUVmean for the whole-body, primary tumor, and regional lymph nodes. The association between each index and patient outcome was assessed using Cox proportional hazards regression. Optimal cut-off points were estimated using recursive binary partitioning in a conditional inference framework and used in Kaplan-Meier curves with log-rank testing. The discriminatory ability of each index was examined using time-dependent receiver operating characteristic (ROC) curves and corresponding area under the curve (AUC(t)). RESULTS: The study included 196 patients. Pretreatment whole-body and primary tumor MTV, TLG, and pvcTLG were independently prognostic of OS. Optimal cut-off points were 175.0, 270.9, and 35.5 cm3 for whole-body TLG, pvcTLG, and MTV, and were 168.2, 239.8, and 17.4 cm3 for primary tumor TLG, pvcTLG, and MTV, respectively. In time-dependent ROC analysis, AUC(t) for MTV and TLG were uniformly higher than that of SUV measures over all time points. Primary tumor and whole-body parameters demonstrated similar patterns of separation for those patients above versus below the optimal cut-off points in Kaplan-Meier curves and in time-dependent ROC analysis. CONCLUSION: We demonstrated that pretreatment whole-body and primary tumor volumetric FDG-PET/CT parameters, including MTV, TLG, and pvcTLG, are strongly prognostic for OS in patients with locally advanced NSCLC, and have similar discriminatory ability. Therefore, we believe that, after validation in future trials, the derived optimal cut-off points for primary tumor volumetric FDG-PET/CT parameters, or their more refined versions, could be incorporated into routine clinical practice, and may provide more accurate prognostication and staging based on tumor metabolic features.

Post-treatment PET/CT and p16 status for predicting treatment outcomes in locally advanced head and neck cancer after definitive radiation.

PURPOSE: To retrospectively review post-treatment (post-tx) FDG-PET/CT scans in patients with advanced head and neck squamous cell carcinoma (HNSCC) and known p16 status, treated with definitive (chemo)radiation (RT). METHODS: A total of 108 eligible patients had N2A or greater HNSCC treated with chemoRT from August 1, 2008, to February 28, 2015, with post-tx PET/CT within 6 months after RT. Kaplan-Meier curves, log-rank statistics, and Cox proportional hazards regression were used for statistical analysis. RESULTS: Median follow-up was 2.38 years. Sixty-eight (63.0%) patients had p16+ and 40 (37.0%) had p16- status. Two-year overall survival and recurrence-free survival were 93.4% and 77.8%, respectively. The negative predictive value (NPV) of PET/CT for local recurrence (LR) was 100%. The NPV for regional recurrence (RR) was 96.5% for all patients, 100% for p16+ patients, and 88.5% for p16- patients. The positive predictive value (PPV) of PET/CT for recurrence was 77.3% for all patients, 50.0% for p16+, and 78.6% for p16-. The PPV for LR was 72.7% for all patients, 50.0% for p16+ patients, and 72.7% for p16- patients. The PPV for RR was 50.0% for all patients, 33% for p16+, and 66.6% for p16-. Post-tx PET/CT and p16 status were independent predictors of recurrence-free survival (p < 0.01). CONCLUSIONS: Post-tx PET/CT predicts treatment outcomes in both p16 + and p16- patients, and does so independently of p16 status. P16- patients with negative PET have a 10% risk of nodal recurrence, and closer follow-up in these patients is warranted.

Prognostic potential of neutrophil-to-lymphocyte ratio and lymphocyte nadir in stage III non-small-cell lung cancer.

AIM: Studies have shown increased pretreatment neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios to be predictive of survival in various cancers. Our aim was to evaluate the prognostic role of such inflammatory markers in non-small-cell lung cancer (NSCLC). METHODS: One hundred and sixty-three patients with stage III NSCLC who received definitive treatment were included. Survival analysis was performed using Kaplan-Meier method. Hazard ratios for overall and recurrence-free survival were estimated using Cox proportional hazards model. RESULTS: Both neutrophil-to-lymphocyte >Q75 (4.5) and lymphocyte nadir values

Outcomes and toxicities in patients treated with definitive focal therapy for primary prostate cancer: systematic review.

AIM: This systematic review summarizes the clinical data on focal therapy (FT) when used alone as definitive therapy for primary prostate cancer (PCa). METHODS: The protocol is detailed in the online PROSPERO database, registration No. CRD42014014765. Articles evaluating any form of FT alone as a definitive treatment for PCa in adult male patients were included. RESULTS: Of 10,419 identified articles, 10,401 were excluded, and thus leaving 18 for analysis. In total, 2288 patients were treated using seven modalities. The outcomes of FT in PCa seem to be similar to those observed with whole gland therapy and with fewer side effects. CONCLUSION: Further research, including prospective randomized trials, is warranted to elucidate the potential advantages of focal radiation techniques for treating PCa. Prospero Registration Number: CRD42014014765.

Development of a Monte Carlo model for treatment planning dose verification of the Leksell Gamma Knife Perfexion radiosurgery system.

Detailed Monte Carlo (MC) modeling of the Leksell Gamma Knife (GK) Perfexion (PFX) collimator system is the only accurate ab initio approach appearing in the literature. As a different approach, in this work, we present a MC model based on film measurement. By adjusting the model parameters and fine-tuning the derived fluence map for each individual source to match the manufacturer's ring output factors, we created a reasonable virtual source model for MC simulations to verify treatment planning dose for the GK PFX radiosurgery system. The MC simulation model was commissioned by simple single shots. Dose profiles and both ring and collimator output factors were compared with the treatment planning system (TPS). Good agreement was achieved for dose profiles especially for the region of plateau (< 2%), while larger difference (< 5%) came from the penumbra region. The maximum difference of the calculated output factor was within 0.7%. The model was further validated by a clinical test case. Good agreement was obtained. The DVHs for brainstem and the skull were almost identical and, for the target, the volume covered by the prescription (12.5 Gy to 50% isodose line) was 95.6% from MC calculation versus 100% from the TPS.

Single versus multiple session stereotactic body radiotherapy for spinal metastasis: the risk-benefit ratio.

Spine stereotactic body radiation therapy represents an important advancement in the management of spinal metastases that allows precise delivery of ablative doses of radiation therapy with excellent local control. Although the technique is being increasingly used in clinical practice, the optimal fractionation schedule remains uncertain. In this perspective paper, we review radiobiologic principles that support the use of multiple- versus single-fraction spine stereotactic body radiation therapy schedules and clinical data supporting the multiple-fraction approach. Specifically, we suggest that there may be a local control benefit of fractionation, while helping to limit the risk of toxicities such as vertebral body fracture, pain flare and radiation myelopathy. We conclude with future directions and the need for future study on this important topic.

Chest wall and rib irradiation and toxicities of early-stage lung cancer patients treated with CyberKnife stereotactic body radiotherapy.

AIM: The aim of the study is to evaluate the chest wall and rib toxicities in primary lung cancer patients treated with CyberKnife-based stereotactic body radiotherapy. MATERIALS & METHODS: In this study, data were collected from the 118 patients, of which 25 patients who had longer follow-up (mean: 21.9 months) were considered. Studied parameters were maximum point dose, doses to 1-100 cm(3) of chest wall and 1-10 cm(3) of ribs. RESULTS: Three patients developed chest wall pain (grade I). 25 studied patients, on average, received 27.7 Gy to 30 cm(3) of chest wall and 50.4 Gy to 1 cm(3) of rib. Nine patients had more than 30 Gy dose to 30 cm(3) of chest wall. No rib bone fracture was found. CONCLUSION: No correlations of chest wall pain and volume of irradiation were found.

Emerging applications of stereotactic body radiotherapy.

Stereotactic body radiotherapy (SBRT) has been used extensively in patients with lung, liver and spinal tumors, and the treatment outcomes are very favorable. For certain conditions such as medically inoperable stage I non-small-cell lung cancer, liver and lung oligometastases, primary liver cancer and spinal metastases, SBRT is regarded as one of the standard therapies. In the recent years, the use of SBRT has been extended to other disease conditions and sites such as recurrent head and neck cancer, renal cell carcinoma, prostate cancer, adrenal metastasis, pancreatic cancer, gynecological malignancies, spinal cord compression, breast cancer, and stage II-III non-small-cell lung cancer. Preliminary data in the literature show promising results but the follow-up intervals are short for most studies. This paper will provide an overview of these emerging applications.

A Pilot Trial of Proton Based Cardiac Sparing Accelerated Fractionated RadioTherapy in Unresectable Non-Small Cell Lung Cancer with Extended Durvalumab Therapy (PARTICLE-D).

PURPOSE: Concurrent chemoradiotherapy is the current non-surgical standard of care for locally advanced non-small cell lung cancer (NSCLC). However, this is a difficult regimen to tolerate especially for those who are elderly, have multiple comorbidities or poor performance status. Alternative treatment regimens are needed for this vulnerable population. We report initial results of concurrent durvalumab, an immune checkpoint inhibitor, and hypofractionated, dose-escalating, proton external beam radiotherapy (EBRT). PATIENTS AND METHODS: This phase I, pilot dose-escalation trial enrolled seven patients with newly diagnosed stage IIIA-IIIC NSCLC who were unable or unwilling to undergo concurrent chemoradiotherapy. Patients previously treated with immunotherapy were excluded. Five patients in the initial phase of this 3+3 study design received a fixed dose of durvalumab each 28-day cycle plus hypofractionated proton EBRT 60 Gy in 20 fractions while two patients received the escalation dose of 69 Gy in 23 fractions. The primary objective assessed safety while secondary objectives assessed feasibility and adverse events. RESULTS: All patients experienced treatment-related adverse events, primarily grades 1-2. Pneumonitis and anemia were the most common. Only one dose limiting toxicity occurred, in arm one, which was a grade 3 pneumonitis leading to grade 5 pneumonia. Additionally, two delayed-onset grade 5 tracheal necrosis events occurred > 13 months after treatment initiation. CONCLUSIONS: Concurrent durvalumab plus hypofractionated proton EBRT was well tolerated in the short term. However, three treatment-related deaths, including two delayed-onset grade 5 tracheal necroses negatively impacted overall safety. A dose de-escalation protocol of proton-based radiotherapy plus durvalumab is warranted.

Outcomes of initial therapy for synchronous brain metastases from small cell lung cancer: a single-institution retrospective analysis.

Small cell lung cancer (SCLC) has a propensity for brain metastases, which is associated with poor prognosis. We sought to determine predictors of overall survival (OS) and brain progression-free survival (bPFS) in SCLC patients with synchronous brain metastases at the time of initial SCLC diagnosis. A total of 107 SCLC patients with synchronous brain metastases treated at a single institution were included in this retrospective analysis. These patients had brain lesions present on initial staging imaging. Survival was estimated using the Kaplan-Meier method with log-rank test. Factors predictive of OS and bPFS were analyzed using Cox proportional hazards regression model. Median OS for the entire cohort was 9 months (interquartile range, 4.2-13.8 months) and median bPFS was 7.3 months (interquartile range, 3.5-11.1 months). OS was 30.3% at 1 year and 14.4% at 2 years, while bPFS was 22.0% at 1 year and 6.9% at 2 years. The median number of brain lesions at diagnosis was 3 (interquartile range, 2-8), and the median size of the largest metastasis was 2.0 cm (interquartile range, 1.0-3.3 cm). Increased number of brain lesions was significantly associated with decreased OS. Patients who received both chemotherapy and whole brain radiation therapy (WBRT) had improved OS (P=0.02) and bPFS (P=0.005) compared to those who had either chemotherapy or WBRT alone. There was no significant difference in OS or bPFS depending on the sequence of therapy or the dose of WBRT. Thirteen patients underwent upfront brain metastasis resection, which was associated with improved OS (P=0.02) but not bPFS (P=0.09) compared to those who did not have surgery. The combination of chemotherapy and WBRT was associated with improved OS and bPFS compared to either modality alone. Upfront brain metastasis resection was associated with improved OS but not bPFS compared to those who did not have surgery.

Single institution experience of MRI-guided radiotherapy for thoracic tumors and clinical characteristics impacting treatment duty cycle.

Introduction: MRI-guided radiotherapy (MRgRT) allows for direct motion management and real-time radiation treatment plan adaptation. We report our institutional experience using low strength 0.35T MRgRT for thoracic malignancies, and evaluate changes in treatment duty cycle between first and final MRgRT fractions. Methods: All patients with intrathoracic tumors treated with MRgRT were included. The primary reason for MRgRT (adjacent organ at risk [OAR] vs. motion management [MM] vs. other) was recorded. Tumor location was classified as central (within 2cm of tracheobronchial tree) vs. non-central, and further classified by the Expanded HILUS grouping. Gross tumor volume (GTV) motion, planning target volume expansions, dose/fractionation, treatment plan time, and total delivery time were extracted from the treatment planning system. Treatment plan time was defined as the time for beam delivery, including multileaf collimator (MLC) motion, and gantry rotation. Treatment delivery time was defined as the time from beam on to completion of treatment, including treatment plan time and patient respiratory breath holds. Duty cycle was calculated as treatment plan time/treatment delivery time. Duty cycles were compared between first and final fraction using a two-sample t-test. Results: Twenty-seven patients with thoracic tumors (16 non-small cell lung cancer and 11 thoracic metastases) were treated with MRgRT between 12/2021 and 06/2023. Fifteen patients received MRgRT due to OAR and 11 patients received MRgRT for motion management. 11 patients had central tumors and all were treated with MRgRT due to OAR risk. The median dose/fractionation was 50 Gy/5 fractions. For patients treated due to OAR (n=15), 80% had at least 1 adapted fraction during their course of radiotherapy. There was no plan adaptation for patients treated due to motion management (n=11). Mean GTV motion was significantly higher for patients treated due to motion management compared to OAR (16.1mm vs. 6.5mm, p=0.011). Mean duty cycle for fraction 1 was 54.2% compared to 62.1% with final fraction (p=0.004). Mean fraction 1 duty cycle was higher for patients treated due to OAR compared to patients treated for MM (61% vs. 45.0%, p=0.012). Discussion: Duty cycle improved from first fraction to final fraction possibly due to patient familiarity with treatment. Duty cycle was improved for patients treated due to OAR risk, likely due to more central location and thus decreased target motion.