Evaluation of knowledge-based planning models for male pelvic CBCT-based online adaptive radiotherapy on conventional linear accelerators.

PURPOSE: To assess the practicality of employing a commercial knowledge-based planning tool (RapidPlan) to generate adapted intact prostate and prostate bed volumetric modulated arc therapy (VMAT) plans on iterative cone-beam computed tomography (iCBCT) datasets. METHODS AND MATERIALS: Intact prostate and prostate bed RapidPlan models were trained utilizing planning data from 50 and 44 clinical cases, respectively. To ensure that refined models were capable of producing adequate clinical plans with a single optimization, models were tested with 50 clinical planning CT datasets by comparing dose-volume histogram (DVH) and plan quality metric (PQM) values between clinical and RapidPlan-generated plans. The RapidPlan tool was then used to retrospectively generate adapted VMAT plans on daily iCBCT images for 20 intact prostate and 15 prostate bed cases. As before, DVH and PQM metrics were utilized to dosimetrically compare scheduled (iCBCT Verify) and adapted (iCBCT RapidPlan) plans. Timing data was collected to further evaluate the feasibility of integrating this approach within an online adaptive radiotherapy workflow. RESULTS: Model testing results confirmed the models were capable of producing VMAT plans within a single optimization that were overall improved upon or dosimetrically comparable to original clinical plans. Direct application of RapidPlan on iCBCT datasets produced satisfactory intact prostate and prostate bed plans with generally improved target volume coverage/conformality and rectal sparing relative to iCBCT Verify plans as indicated by DVH values, though bladder metrics were marginally increased on average. Average PQM values for iCBCT RapidPlans were significantly improved compared to iCBCT Verify plans. The average time required [in mm:ss] to generate adapted plans was 06:09 ± 02:06 (intact) and 07:12 ± 01:04 (bed). CONCLUSION: This study demonstrated the feasibility of leveraging RapidPlan to expeditiously generate adapted VMAT intact prostate and prostate bed plans on iCBCT datasets. In general, adapted plans were dosimetrically improved relative to scheduled plans, emphasizing the practicality of the proposed approach.

Chemoimmunotherapy in patients with extensive-stage small cell lung cancer and a poor performance status.

BACKGROUND: Immune checkpoint inhibitor combined with platinum-etoposide is the standard first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC). The phase 3 clinical trials that led to the approval of chemoimmunotherapy in ES-SCLC excluded patients who had an Eastern Cooperative Group (ECOG) performance status (PS) of 2-3. Therefore, data on the efficacy of chemoimmunotherapy in patients with an ECOG PS of 2-3 are limited. METHODS: A retrospective analysis was performed on patients diagnosed with ES-SCLC who received chemoimmunotherapy (atezolizumab or durvalumab) within the Mayo Clinic Health System between January 2016 and January 2021. The objective of this study was to compare the overall survival (OS), progression-free survival (PFS), and best clinical response to therapy in patients with an ECOG PS of 0-1 vs. patients with an ECOG PS of 2-3 who received chemoimmunotherapy for newly diagnosed ES-SCLC. RESULTS: In total, 82 patients were included in the study. The mean ± standard deviation age was 68.1 ± 8.3 years. Of these, 56 patients were identified with an ECOG PS of 0-1, and 26 patients were identified with an ECOG PS of 2-3. The median PFS was similar regardless of ECOG PS (5.8 months [95% CI, 4.3-6.0 months] in the ECOG PS 0-1 group vs. 4.1 months [95% CI, 3.8-6.9 months] in the ECOG PS 2-3; p = .2994). The median OS was also similar regardless of ECOG PS (10.6 months [95% CI, 8.4-13.4 months] in the ECOG PS 0-1 group vs. 9.3 months [95% CI, 4.9-12.8 months]; p = .2718) in the ECOG PS 2-3 group. CONCLUSIONS: The study results demonstrated no significant difference in PFS or OS among the ECOG PS 2-3 and ECOG PS 0-1 groups. Therefore, chemoimmunotherapy should be considered for patients who have ES-SCLC with an ECOG PS of 2-3.

Role of Prophylactic Cranial Irradiation in Extensive-Stage Small Cell Lung Cancer.

Patients with small cell lung cancer (SCLC) are at significant risk of developing brain metastases during their disease course. Prophylactic cranial irradiation (PCI) has been incorporated into SCLC treatment guidelines to diminish the risk of developing brain metastases. In 2007, a randomized trial suggested that PCI decreases the incidence of brain metastases and prolongs overall survival (OS) in patients with extensive-stage SCLC (ES-SCLC) who have responded to initial therapy. However, this study did not include modern central nervous system imaging with CT or MRI prior to randomization. A more recent Japanese trial with MRI staging and surveillance demonstrated that PCI diminished the incidence of brain metastases but did not improve survival. This review examines the largest clinical studies, controversies, and future directions of PCI in patients with ES-SCLC.

Dosimetric comparison of distal esophageal carcinoma plans for patients treated with small-spot intensity-modulated proton versus volumetric-modulated arc therapies.

BACKGROUND: Esophageal carcinoma is the eighth most common cancer in the world. Volumetric-modulated arc therapy (VMAT) is widely used to treat distal esophageal carcinoma due to high conformality to the target and good sparing of organs at risk (OAR). It is not clear if small-spot intensity-modulated proton therapy (IMPT) demonstrates a dosimetric advantage over VMAT. In this study, we compared dosimetric performance of VMAT and small-spot IMPT for distal esophageal carcinoma in terms of plan quality, plan robustness, and interplay effects. METHODS: 35 distal esophageal carcinoma patients were retrospectively reviewed; 19 patients received small-spot IMPT and the remaining 16 of them received VMAT. Both plans were generated by delivering prescription doses to clinical target volumes (CTVs) on phase-averaged 4D-CT's. The dose-volume-histogram (DVH) band method was used to quantify plan robustness. Software was developed to evaluate interplay effects with randomized starting phases for each field per fraction. DVH indices were compared using Wilcoxon rank-sum test. For fair comparison, all the treatment plans were normalized to have the same CTVhigh D95% in the nominal scenario relative to the prescription dose. RESULTS: In the nominal scenario, small-spot IMPT delivered statistically significantly lower liver Dmean and V30Gy[RBE] , lung Dmean , heart Dmean compared with VMAT. CTVhigh dose homogeneity and protection of other OARs were comparable between the two treatments. In terms of plan robustness, the IMPT and VMAT plans were comparable for kidney V18Gy[RBE] , liver V30Gy[RBE] , stomach V45Gy[RBE] , lung Dmean , V5Gy[RBE] , and V20Gy[RBE] , cord Dmax and D 0.03 c m 3 , liver Dmean , heart V20Gy[RBE] , and V30Gy[RBE] , but IMPT was significantly worse for CTVhigh D95% , D 2 c m 3 , and D5% -D95% , CTVlow D95% , heart Dmean , and V40Gy[RBE] , requiring careful and experienced adjustments during the planning process and robustness considerations. The small-spot IMPT plans still met the standard clinical requirements after interplay effects were considered. CONCLUSIONS: Small-spot IMPT decreases doses to heart, liver, and total lung compared to VMAT as well as achieves clinically acceptable plan robustness. Our study supports the use of small-spot IMPT for the treatment of distal esophageal carcinoma.

The Role of Radiotherapy for Meningeal Melanocytomas - A 20 Year Update.

BACKGROUND/AIM: Meningeal melanocytomas are rare tumors of the central nervous system and optimal treatment needs further clarification. This study compared subtotal resection (STR), STR plus radiation therapy (RT), gross total resection (GTR), and GTR+RT to better define the role of postoperative RT. PATIENTS AND METHODS: All cases reported in the literature were reviewed. Patients (n=184) with complete data were analyzed for local control (LC) and overall survival (OS). RESULTS: On univariate analysis, GTR (vs. STR) was associated with improved LC (p=0.016). When comparing the treatment regimens, best and worst results were found after GTR+RT and STR alone, respectively (p<0.001). On univariate analysis, GTR resulted in better OS than STR (p=0.041). Moreover, the treatment regimen had a significant impact on OS (p=0.049). On multivariate analyses of LC and OS, extent of resection and treatment regimen were found to be significant factors. After STR, RT significantly improved LC but not OS. After GTR, RT did not significantly improve LC or OS. CONCLUSION: GTR was significantly superior to STR regarding LC and OS. STR+RT resulted in significantly better LC when compared to STR alone.

Prognostic Factors for Progression-free Survival and Overall Survival After Recurrence of Glioblastoma.

BACKGROUND/AIM: Many patients with glioblastoma experience an intracerebral recurrence and require a personalized treatment. This study aimed to facilitate this approach by identifying prognostic factors for progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: In 102 patients with recurrent glioblastoma following primary treatment with resection or biopsy plus adjuvant chemoradiation, 11 characteristics were retrospectively investigated regarding PFS and OS. RESULTS: In the multivariate analyses, Karnofsky performance score (KPS) 90-100 at the time of recurrence (p=0.032), maximum cumulative diameter of recurrent lesions ≤40 mm (p=0.002), resection of recurrent glioblastoma (p=0.025), and systemic therapy for recurrent glioblastoma (p=0.025) were significantly associated with improved PFS. In addition, KPS 90-100 (p=0.024), maximum cumulative diameter ≤40 mm (p=0.033), and systemic therapy (p=0.006) were significantly associated with better OS. CONCLUSION: Our study identified high Karnofsky Performance Status (KPS 90-100), maximum cumulative diameter of recurrent glioblastoma lesions ≤40 mm, and systemic therapy for recurrent glioblastoma as independent predictors of overall survival (OS) and progression-free survival (PFS). These independent prognostic factors may help select the most suitable treatment for individual patients with recurrent glioblastoma, potentially improving patient outcomes.

Distress Scores in Elderly Cancer Patients During Radiotherapy.

BACKGROUND/AIM: When assigned to radiotherapy (RT), elderly patients may experience distress. We investigated distress during RT and potential risk factors in these patients. PATIENTS AND METHODS: Six-hundred-and-nineteen patients completed pre-RT and post-RT distress thermometers. Seven characteristics were investigated including age, sex, Karnofsky performance score (KPS), grouped KPS, tumor type, intent of RT, and previous RT. Additional analyses were performed in 358 patients with pre-RT scores ≤5. RESULTS: Mean change of distress was -0.5 (±2.7) points and associated with KPS (p=0.005) and grouped KPS (p<0.001). Male sex (p=0.035), KPS 90-100 (p=0.001), and curative intent (p=0.037) were associated with increased distress on univariable analyses, and KPS 90-100 (odds ratio=1.92, p=0.004) on multivariable analysis. In patients with baseline scores ≤5, mean change was +0.5 (±2.5) points and associated with KPS (p=0.040) and grouped KPS (p=0.025). CONCLUSION: Psychological assistance should be considered for all patients including those with baseline scores ≤5 and KPS 90-100. Patients with risk factors for increased distress would especially benefit.

The Predictive Value of Different Glasgow Prognostic Scores and the LabBM Score for Patients With Recurrent Glioblastoma.

BACKGROUND/AIM: The prognostic value of scoring instruments was described for newly diagnosed glioblastoma. This study investigated five instruments in patients with recurrent tumors. PATIENTS AND METHODS: Original Glasgow Prognostic Score (oGPS), modified GPS (mGPS), high-sensitivity mGPS (HS-mGPS), high-sensitivity oGPS (HS-oGPS), LabBM score, and 10 other factors were analyzed for progression-free survival (PFS) and overall survival (OS) in 51 patients. RESULTS: On univariate analyses, oGPS 0-1, mGPS 0-1, and LabBM score 0-1.0 were significantly associated with improved OS and showed trends for improved PFS. On multivariate analysis, a trend was found for associations between LabBM score 0-1.0 and better OS. In addition, maximal cumulative diameter ≤40 mm and systemic therapy were independently associated with better PFS and OS, resection with PFS, and in-field recurrence with OS. CONCLUSION: Lower oGPS, mGPS, and LabBM scores were significantly associated with improved OS on univariate analyses. These instruments may be helpful when designing personalized treatment regimens for patients with recurrent glioblastoma.

Prognostic Role of Platelet-to-Lymphocyte and Neutrophil-to-Lymphocyte Ratios in Patients Irradiated for Glioblastoma Multiforme.

Background/Aim: Previous studies suggested pre-operative platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) to be predictive factors in patients with glioblastoma multiforme (GBM). This study investigated the prognostic role of PLR and NLR prior to or at the beginning of radiotherapy. Patients and Methods: In 80 patients with GBM receiving conventionally fractionated radiotherapy plus concurrent temozolomide following resection or biopsy, 12 factors including PLR and NLR were retrospectively evaluated regarding progression-free survival (PFS) and overall survival (OS). Results: On multivariable analyses, PLR ≤150, Karnofsky performance score (KPS) 90-100, and O6-methylguanine-DNA methyltransferase promoter methylation were significantly associated with improved PFS. Single lesion, KPS 90-100, and adjuvant chemotherapy were significantly associated with OS; PLR ≤150 showed a trend. NLR ≤3 showed a trend for associations with PFS and OS on univariable analyses. Conclusion: PLR prior to or at the beginning of radiotherapy was associated with treatment outcomes in patients irradiated for GBM and should be considered in future clinical trials.

Evaluation of Five Prognostic Scores in Patients Receiving Chemoradiation for Primary Glioblastoma Multiforme.

BACKGROUND/AIM: Prognostic factors can facilitate treatment personalization in patients with glioblastoma multiforme (GBM). This study investigated different Glasgow prognostic scores (GPS) and the LabBM score in patients with GBM receiving chemoradiation following resection or biopsy. PATIENTS AND METHODS: Four GPS versions, LabBM score, and 10 other factors were retrospectively investigated for progression-free survival (PFS) and overall survival (OS) in 86 patients. GPS versions included original GPS (oGPS), modified GPS (mGPS), high-sensitivity mGPS (HS-mGPS), and high-sensitivity oGPS (HS-oGPS). RESULTS: On multivariate analysis, higher oGPS was significantly associated with worse OS (p=0.006). On univariate analyses, trends were found for associations between higher mGPS and worse OS (p=0.098) and between higher LabBM scores and worse PFS (p=0.059). CONCLUSION: The oGPS was an independent predictor of OS in patients receiving chemoradiation for GBM and can help personalizing the treatment for these patients. The LabBM score may be useful for predicting PFS.

Can Platelet-to-Lymphocyte Ratio (PLR) and Neutrophil-to-Lymphocyte Ratio (NLR) Help Predict Outcomes of Patients With Recurrent Glioblastoma?

BACKGROUND/AIM: In patients with recurrent glioblastoma, very little data are available regarding the prognostic value of platelet-to-lymphocyte (PLR) and neutrophil-to-lymphocyte (NLR) ratios. This study investigated potential associations between PLR or NLR and treatment outcomes. PATIENTS AND METHODS: PLR and NLR at diagnosis of recurrence plus 10 additional characteristics were retrospectively analyzed for associations with progression-free survival (PFS) and overall survival (OS) in 75 patients with recurrent glioblastoma. RESULTS: On multivariate analyses, maximal cumulative diameter of recurrent lesion(s) <40 mm (p=0.015) and systemic therapy (p<0.001) were associated with improved PFS. On multivariate analysis of OS, improved outcomes were significantly associated with PLR ≤150 (p=0.029), maximal cumulative diameter <40 mm (p=0.030), and systemic therapy (p=0.010). CONCLUSION: In addition to other characteristics, PLR at the time of recurrence was identified as an independent predictor of OS in patients with recurrent glioblastoma. PLR may be useful when designing personalized treatment approaches or clinical trials.

Clinically Significant Dermatitis During Adjuvant Radiotherapy for Invasive Breast Cancer.

BACKGROUND/AIM: Patients with breast cancer receiving adjuvant radiotherapy may experience grade ≥2 dermatitis. In the Interreg-project HeAT, a mobile application (app) reminding patients to perform skin care will be prospectively tested with the goal of decreasing clinically significant radiation dermatitis. This study aimed to identify the prevalence of grade ≥2 dermatitis and risk factors, required for designing the prospective trial. PATIENTS AND METHODS: In a retrospective study of 327 patients with breast cancer irradiated during 2022-2023, the prevalence of grade ≥2 dermatitis and 23 potential risk factors were investigated. RESULTS: The prevalence of grade ≥2 dermatitis was 31.2%. On multivariate analysis, it was significantly associated with chronic inflammatory disease (p=0.001), significant cardiovascular disease (p<0.001), smoking history >10 pack years (p<0.001), advanced T-stage (p=0.017), normo-fractionation (p<0.001), and radiation boost (p<0.001). CONCLUSION: The prevalence of grade ≥2 dermatitis and independent risk factors during adjuvant radiotherapy for invasive breast cancer were identified that contribute to improved patient care and the design of a prospective trial.

Associations Between Mean Lung Dose and Prevalence of Radiation Pneumonitis in Elderly Lung Cancer Patients.

BACKGROUND/AIM: Pneumonitis is a serious radiotherapy complication. This study, which is a prerequisite for a prospective trial, aimed to identify the prevalence of pneumonitis and risk factors in elderly patients with lung cancer. PATIENTS AND METHODS: Ninety-eight lung cancer patients aged ≥65 years were included. Seventeen factors were investigated regarding grade ≥2 pneumonitis at 24 weeks following radiotherapy. RESULTS: The prevalence of grade ≥2 pneumonitis at 24 weeks was 27.3%. On univariate analysis, a significant association was observed for mean (ipsilateral) lung dose (MLD; ≤13.0 vs. 13.1-20.0 vs. >20.0 Gy; 0% vs. 24.9% vs. 48.7%). Results were significant also for ≤13.0 vs. >13.0 Gy (0% vs. 37.1%) or ≤20.0 vs. >20.0 Gy (13.4% vs. 48.7%). MLD achieved significance on multivariate analysis. CONCLUSION: Elderly patients receiving MLDs >13.0 Gy, particularly >20.0 Gy, have a high risk of grade ≥2 pneumonitis. These results are important for designing a prospective trial.

Seasonal Impact on Grade ≥2 Dermatitis in Patients With Breast Cancer Undergoing Radiotherapy: A Supplementary Analysis.

BACKGROUND/AIM: We investigated grade ≥2 dermatitis in patients irradiated for breast cancer. This study evaluated associations between dermatitis and the season during which radiotherapy took place. PATIENTS AND METHODS: Associations between the season and grade ≥2 dermatitis were retrospectively evaluated in 327 breast cancer patients. Seasons were March to May (spring), June to August (summer), September to November (autumn), and December to February (winter). Subgroup analyses were performed considering fractionation, radiation technique, treatment volume, radiation boost, and deep-inspiration breath-hold technique. Furthermore, warmer and cooler months were compared. RESULTS: The season had no significant impact on the rate of grade ≥2 dermatitis in the entire cohort (p=0.63) nor in the subgroup analyses (p-values between 0.17 and 0.82). No significant difference in rate was found between warm and cool months. CONCLUSION: Grade ≥2 dermatitis was not associated with the season during which radiotherapy was performed. This factor may not be important for stratification in prospective trials.

Caught Between a Radiation Oncology Case Rate (ROCR) and a Hard Place: Improving Proposed Radiation Oncology Alternative Payment Models.

PURPOSE: The Radiation Oncology Case Rate (ROCR) aims to shift radiation reimbursement from fee-for-service (FFS) to bundled payments, which would decouple fractionation from reimbursement in the United States. This study compares historical reimbursement rates from 3 large centers and a national Medicare sample with proposed base rates from ROCR. It also tests the impact of methodological inclusion of treatment and disease characteristics to determine if any variables are associated with greater rate differences that may lead to inequitable reimbursement. METHODS AND MATERIALS: Using Mayo Clinic electronic medical record data from 2017 to 2020 and part B claims from the Medicare 5% research identifiable files, episodic 90-day historical reimbursement rates for 15 cancer types were calculated per the ROCR payment methodology. Mayo Clinic reimbursement rates were stratified by disease and treatment characteristics and multiple linear regression was performed to assess the association of these variables on historical episode reimbursement rates. RESULTS: From Mayo Clinic, 3498 patient episodes were included and 480,526 from the research identifiable files. From both data sets, 25% of brain metastases and 13% of bone metastases episodes included ≥2 treatment courses with an average of 51 days between courses. Accounting for all 15 cancer types, ROCR base rates resulted in an average -2.4% and -2.9% reduction in rates for Mayo Clinic and the research identifiable files respectively compared with historical reimbursement. On multivariate analysis of Mayo Clinic data, treatment intent (curative vs palliative) was associated with higher historical reimbursement (+$477 to +$7417; P ≤.05) for 12 out of 12 applicable cancer types. Stage (III-IV vs I-II) was associated with higher historical reimbursement (+$1169 to +$3917; P ≤ .05) for 8 out of 12 applicable cancer types. CONCLUSIONS: Our data suggest ROCR base rates introduce an average ≤3% reimbursement rate decrease compared with historical FFS reimbursement per cancer type, which could produce the Medicare savings required for congressional approval of ROCR. Estimating comparisons with future FFS reimbursement would require consideration of additional factors such as the increased utilization of hypofractionation, proposed FFS rate cuts, and inflationary updates. A distinct rate and shortened episode duration (≤30 days) should be considered for palliative episodes. Applying a base rate modifier per cancer stage may mitigate disproportionate reductions in reimbursement for facilities with a higher volume of curative advanced-stage patients such as freestanding centers in rural settings.