Difference in failure patterns after stereotactic body radiotherapy for lung cancer according to clinical T stage based on 4D computed tomography.

PURPOSE: Stereotactic body radiotherapy (SBRT) is a treatment option for early-stage lung cancer. We aimed to examine the differences in failure patterns after SBRT according to the clinical T stage. METHODS: A total of 120 patients with early-stage lung cancer (T1-3N0M0) who underwent SBRT were analysed. The clinical stage in patients whose tumours were in contact with the chest wall was confirmed using four-dimensional computed tomography (4D-CT). Local failure, regional node metastasis, and distant metastasis were confirmed from clinical charts. RESULTS: Median follow-up time was 27.5 months (range 7-122) after SBRT. Thirteen patients were restaged from clinical T2 with visceral pleural invasion to T3 with chest wall invasion using 4D-CT analysis. Thirty-seven patients developed recurrences. The median progression-free survival (PFS) and overall survival (OS) were 38.1 and 53.8 months, respectively. The 3­year PFS and OS rates were 50.7% and 60.3%, respectively. A significant difference was observed in PFS according to the clinical T stage (p = 0.001). No significant differences were observed in OS according to the clinical T stage (p = 0.213). The proportion of locoregional failures relative to distant metastasis decreased with progression from T1 to T3. The pleural dissemination rate was significantly higher in T3 tumours than in T1 and T2 tumours (p = 0.010). CONCLUSION: Clinical T stage is associated with PFS after SBRT for lung cancer. There were differences in the failure patterns according to T stage. 4D-CT might provide significant information for assessing chest wall invasion associated with unfavourable PFS.

External beam radiotherapy combination is a risk factor for bladder cancer in patients with prostate cancer treated with brachytherapy.

PURPOSE: To investigate the risk of bladder cancer (BCa) in patients treated with brachytherapy for prostate cancer (PCa). METHODS: We retrospectively analyzed 583 patients with PCa who underwent brachytherapy with or without external beam radiotherapy (EBRT). We analyzed the disease-free survival (DFS) of BCa in patients with PCa who underwent brachytherapy with or without EBRT. We performed multivariate Cox regression analyses of DFS using age, EBRT, and Brinkman index (BI) score (number of cigarettes smoked per day × number of years smoking) ≥ 200 as variables for BCa after brachytherapy. RESULTS: Fourteen patients (2.4%) developed BCa after brachytherapy with or without EBRT. The percentage of high-grade urothelial carcinoma (UC) was 63.6%. A total of 85.7% of patients had non-muscle invasive BCa, and 14.3% of patients had muscle invasive BCa. DFS was longer in brachytherapy monotherapy than in combination therapy (brachytherapy + EBRT). Multivariate Cox regression analysis showed that a BI score ≥ 200 (Hazard Ratio (HR 8.61; 95% Confidence Interval (CI) 1.12-65.98) and EBRT combination (HR 3.29; 95% CI 1.03-10.52) were significantly associated with BCa development in patients with PCa treated with brachytherapy. Furthermore, patients with BI score ≥ 200 and EBRT combination had a significantly higher risk of BCa compared with patients with BI score < 200 (HR Log-rank test P = 0.010). CONCLUSION: Most cases of BCa after brachytherapy with or without EBRT are high grade and invasive. We hypothesized that the EBRT combination might be a risk factor for BCa in patients with PCa who underwent brachytherapy.

Clinical course of longer than five years after definitive radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: This study aimed to reveal the long-term outcomes and late toxicities (> 5 years) after definitive intensity-modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). METHODS: Data from 43 patients (median age, 55 years; range, 17-72 years) with NPC who underwent definitive IMRT between 2001 and 2018 were analyzed. All patients were alive and disease-free 5 years after IMRT. A total dose of 70 (range, 66-70) Gy was delivered in 35 (33-35) fractions with concurrent cisplatin chemotherapy. RESULTS: The median follow-up duration was 119 (range, 61.5-242.1) months. Three patients developed locoregional failure at 79, 92, and 149 months after IMRT, respectively. Of these, 2 patients died of disease progression at 136 and 153 months after IMRT. One patient died of aspiration pneumonia 141 months after IMRT, despite salvage of the recurrent tumor by re-irradiation. In addition, one patient died of aspiration pneumonia 62 months after the IMRT. Thus, the 10-year overall survival, progression-free survival, and locoregional control rates were 98%, 92%, and 94%, respectively. Grade ≥ 2 and ≥ 3 late toxicities were observed in 28 (65%) and 9 (21%) patients, respectively. Nine second primary cancers, including five tongue cancers and two external auditory canal carcinomas, were observed in seven (16%) patients. CONCLUSION: Late recurrences, severe late toxicities, and second primary cancers were observed > 5 years after IMRT. A long-term follow-up of > 5 years is needed in patients with NPC.

Multi-institutional feasibility study of intensity-modulated radiotherapy with chemotherapy for locally advanced non-small cell lung cancer.

BACKGROUND: This multi-institutional clinical trial evaluated the feasibility of intensity-modulated radiotherapy (IMRT) for patients with locally advanced non-small cell lung cancer (NSCLC). METHODS: The major inclusion criteria were clinical stage III NSCLC, age 20-74 years, and Eastern Cooperative Oncology Group performance status 0-1. Patients were treated with either cisplatin + S-1 (CS; four cycles every 4 weeks) or carboplatin + paclitaxel (CP; administered weekly with thoracic radiotherapy [RT], plus two consolidation cycles) concurrently with IMRT (60 Gy in 30 fractions). The primary endpoint was a treatment completion rate, defined as at least two cycles of CS or five cycles of CP during IMRT and completing 60 Gy IMRT within 56 days after the start of treatment, assumed its 90% confidence interval exceeds 60%. RT quality assurance was mandatory for all the patients. RESULTS: Twenty-two patients were registered. One patient withdrew due to pulmonary infection before starting treatment. RT plans were reviewed and none was judged as a protocol violation. Grade 2 and 3 pneumonitis occurred in four (19%) and one (5%) patients, respectively. Seventeen patients met the primary endpoint, with a treatment completion rate of 77.3% (90% confidence interval [CI] 58.0%-90.6%). Four patients failed to complete chemotherapy due to chemotherapy-related adverse events, but 20 patients completed IMRT. There were no treatment-related deaths. The 2-year progression-free and overall survival rates were 31.8% (95% CI 17.3%-58.7%) and 77.3% (95% CI 61.6%-96.9%), respectively. CONCLUSION: The treatment completion rate did not meet the primary endpoint, but 20 of 22 patients completed IMRT.

An updating approach for knowledge-based planning models to improve plan quality and variability in volumetric-modulated arc therapy for prostate cancer.

PURPOSE: The purpose of this study was to compare the dose-volume parameters and regression scatter plots of the iteratively improved RapidPlan (RP) models, specific knowledge-based planning (KBP) models, in volumetric-modulated arc therapy (VMAT) for prostate cancer over three periods. METHODS: A RP1 model was created from 47 clinical intensity-modulated radiation therapy (IMRT)/VMAT plans. A RP2 model was created to exceed dosimetric goals which set as the mean values +1SD of the dose-volume parameters of RP1 (50 consecutive new clinical VMAT plans). A RP3 model was created with more strict dose constraints for organs at risks (OARs) than RP1 and RP2 models (50 consecutive anew clinical VMAT plans). Each RP model was validated against 30 validation plans (RP1, RP2, and RP3) that were not used for model configuration, and the dose-volume parameters were compared. The Cook's distances of regression scatterplots of each model were also evaluated. RESULTS: Significant differences (p < 0.05) between RP1 and RP2 were found in Dmean (101.5% vs. 101.9%), homogeneity index (3.90 vs. 4.44), 95% isodose conformity index (1.22 vs. 1.20) for the target, V40Gy (47.3% vs. 45.7%), V60Gy (27.9% vs. 27.1%), V70Gy (16.4% vs. 15.2%), and V78Gy (0.4% vs. 0.2%) for the rectal wall, and V40Gy (43.8% vs. 41.8%) and V70Gy (21.3% vs. 20.5%) for the bladder wall, whereas only V70Gy (15.2% vs. 15.8%) of the rectal wall differed significantly between RP2 and RP3. The proportions of cases with a Cook's distance of <1.0 (RP1, RP2, and RP3 models) were 55%, 78%, and 84% for the rectal wall, and 77%, 68%, and 76% for the bladder wall, respectively. CONCLUSIONS: The iteratively improved RP models, reflecting the clear dosimetric goals based on the RP feedback (dose-volume parameters) and more strict dose constraints for the OARs, generated superior dose-volume parameters and the regression scatterplots in the model converged. This approach could be used to standardize the inverse planning strategies.

Outcome of chemoradiotherapy using intensity-modulated radiation therapy for cervical esophageal cancer: a single institute experience.

BACKGROUND: The role of intensity-modulated radiation therapy in the treatment of cervical esophageal cancer remains unclear. The outcome of concurrent chemoradiotherapy for cervical esophageal squamous cell carcinoma using intensity-modulated radiation therapy was retrospectively evaluated. METHODS: Between 2004 and 2017, 36 patients with cervical esophageal cancer treated with intensity-modulated radiation therapy were included. Among these patients, one had stage II disease, three stage III, 19 stage IVA, and 13 stage IVB. All patients received radiotherapy at a dose of 60 Gy and concurrent platinum-based doublet chemotherapy. RESULTS: The median follow-up period for surviving patients was 36 months. Three-year locoregional control, progression-free survival, and overall survival rates were 54, 40, and 46%, respectively. Disease progression was noted in 20 out of 36 patients (56%). Grade 3 late toxicities were observed in four patients (three esophageal stenoses and one carotid artery stenosis). There were no grade 4-5 toxicities. Univariate analysis identified the duration of radiotherapy as a prognostic factor for overall survival. CONCLUSIONS: Chemoradiotherapy using intensity-modulated radiation therapy for locally advanced cervical esophageal carcinoma achieved satisfactory locoregional control and survival with acceptable toxicities.

[Impact of Aperture Shape Controller on Knowledge-based VMAT Planning of Prostate Cancer].

PURPOSE: Knowledge-based planning (KBP) has disadvantages of high monitor unit (MU) and complex multi-leaf collimator (MLC) motion. We investigated the optimal aperture shape controller (ASC) level for the KBP to reduce these factors in volumetric modulated arc therapy (VMAT) for prostate cancer. METHODS: The KBP model was created based on 51 clinical plans (CPs) of patients who underwent the VMAT for prostate cancer. Another 10 CPs were selected randomly, and the KBPs with/without ASC, changed stepwise from very low (KBP-VL) to very high (KBP-VH), were performed with a single auto-optimization. The parameters of dose-volume histograms (DVHs) and MLC performance metrics were evaluated. We obtained the modulation complexity score for VMAT (MCSv), closed leaf score (CLS), small aperture score (SAS), leaf travel (LT), and total MU. RESULTS: The ASC did not affect the DVH parameters negatively. The following comparisons of MLC performance were obtained (KBP vs. KBP-VL vs. KBP-VH, respectively): 0.25 vs. 0.27 vs. 0.30 (MCSv), 0.19 vs. 0.18 vs. 0.16 (CLS), 0.50 vs. 0.45 vs. 0.40 (SAS10 mm), 0.73 vs. 0.68 vs. 0.63 (SAS20 mm), 768.35 mm vs. 671.50 mm vs. 551.32 mm (LT), and 672.87 vs. 642.36 vs. 607.59 (MU). There were significant differences between KBP and KBP-VH for MCSv and LT (p<0.05). CONCLUSIONS: The KBP using an ASC set to the very high level could reduce the complexity of MLC motion significantly more without deterioration of the DVH parameters compared with the KBP in VMAT for prostate cancer.

Stereotactic body radiotherapy in patients with chronic obstructive pulmonary disease and interstitial pneumonia: a review.

Stereotactic body radiation therapy (SBRT) can yield excellent local tumor control, as well as survival benefit comparable to that of surgery for early-stage lung cancer. However, in terms of toxicity, SBRT might lead to fatal radiation pneumonitis. Lung diseases, such as chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), are major risk factors for lung cancer. However, these patients are typically not candidates for the gold-standard treatment option, lobectomy, because of the perioperative risks. In addition, patients with poor respiratory function can be excluded in prospective clinical trials. Thus, SBRT for patients with pulmonary diseases is still challenging, but there appears to be a clinical role for this modality as an alternative treatment. However, there are few well-documented review articles on SBRT for patients with pulmonary diseases. Therefore, we aimed to review SBRT in the context of important patient-related factors, including COPD and ILD. SBRT is an acceptable alternative treatment option for patients with lung cancer who also have COPD with an equivalent risk of radiation pneumonitis to normal lung. However, latent ILD should be detected prior to treatment. The indication for SBRT should be decided by carefully considering the risks and benefit for patients with ILD.

Comparing the 7th and 8th editions of the American Joint Committee on Cancer/Union for International Cancer Control TNM staging system for esophageal squamous cell carcinoma treated by definitive radiotherapy.

BACKGROUND: We retrospectively compared the 7th and the 8th editions of The American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM classification in the cohort of survival of the patients with esophageal squamous cell carcinoma (ESCC) treated by definitive radiotherapy. METHODS: We included in this study 403 patients with ESCC who underwent radiotherapy or chemoradiotherapy, at a total radiation dose of ≥ 50 Gy with curative intent from 2000 to 2016 at Kindai University Hospital, and who had no distant metastasis (excluding supraclavicular lymph node). The same patient data set was re-staged according to both the 7th and 8th editions of AJCC/UICC TNM classification. RESULTS: For the 7th edition, 5-year overall survival (OS) for stages I, II, III, and IV were 58%, 52%, 22%, and 12%, respectively, which seemed to be separable into two groups (Stages I-II and III-IV). In the 8th edition, corresponding values for stages I, II, III, and IV were 65%, 44%, 34%, and 16%, respectively, which seemed to be separated into three groups (Stage I, II-III, and IV). CONCLUSIONS: The 8th edition of AJCC/UICC TNM classification is a useful predictor of OS among ESCC patients who were treated with definitive radiotherapy.

Comparison of patient-specific intensity modulated radiation therapy quality assurance for the prostate across multiple institutions.

AIM: To evaluate the success of a patient-specific intensity modulated radiation therapy (IMRT) quality assurance (QA) practice for prostate cancer patients across multiple institutions using a questionnaire survey. BACKGROUND: The IMRT QA practice involves different methods of dose distribution verification and analysis at different institutions. MATERIALS AND METHODS: Two full-arc volumetric modulated arc therapy (VMAT) plan and 7 fixed-gantry IMRT plan with DMLC were used for patient specific QA across 22 institutions. The same computed tomography image and structure set were used for all plans. Each institution recalculated the dose distribution with fixed monitor units and without any modification. Single-point dose measurement with a cylindrical ionization chamber and dose distribution verification with a multi-detector or radiochromic film were performed, according to the QA process at each institution. RESULTS: Twenty-two institutions performed the patient-specific IMRT QA verifications. With a single-point dose measurement at the isocenter, the average difference between the calculated and measured doses was 0.5 ±â€¯1.9%. For the comparison of dose distributions, 18 institutions used a two or three-dimensional array detector, while the others used Gafchromic film. In the γ test with dose difference/distance-to-agreement criteria of 3%-3 mm and 2%-2 mm with a 30% dose threshold, the median gamma pass rates were 99.3% (range: 41.7%-100.0%) and 96.4% (range: 29.4%-100.0%), respectively. CONCLUSION: This survey was an informative trial to understand the verification status of patient-specific IMRT QA measurements for prostate cancer. In most institutions, the point dose measurement and dose distribution differences met the desired criteria.

Definitive chemoradiotherapy for anal canal cancer: single-center experience.

BACKGROUND: Chemoradiotherapy (CRT) is a standard treatment for anal canal cancer although many patients with anal canal cancer undergo surgery in Japan. The efficacy of CRT for anal canal cancer was evaluated retrospectively. METHODS: Medical charts of 13 patients with anal canal cancer treated by definitive CRT from October 2004 to May 2016 were reviewed. Twelve patients had squamous cell carcinoma and one had adeno-squamous carcinoma. PET/CT simulation was performed in nine patients. The median total dose was 59.4 Gy (range 57.6-63.4 Gy) with fractions of 1.8-2.0 Gy. Ten patients received chemotherapy with mitomycin C (10 mg/m2) and fluorouracil (5-FU) (800 mg/m2 over 4 days) in weeks 1 and 5, while two patients were treated with cisplatin (40 mg) and 5-FU (750 mg over 5 days) in weeks 1 and 5. One elderly patient received radiotherapy (RT) alone. RESULTS: All 13 patients were alive after a median follow-up period of 102 months (range 16-121 months). Local failure only occurred in the patient with adeno-squamous cell carcinoma, while there was no loco-regional recurrence or distant metastasis in the other 12 patients. The 5-year loco-regional control rate (LRC) and 5-year overall survival rate (OS) were 92% and 100%, respectively. Acute toxicities of ≥ grade 3 were observed in six patients (46%), mainly being dermatitis around the anal verge, and late toxicity of ≥ grade 3 occurred in one patient. CONCLUSION: CRT for squamous cell carcinoma of the anal canal achieved good LRC and OS with acceptable toxicities.

Clinical outcomes of IMRT planned with or without PET/CT simulation for patients with pharyngeal cancers.

BACKGROUND: Clinical results of computed tomography (CT) simulations and [18F]-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT simulations were compared retrospectively. MATERIALS AND METHODS: Between 2006 and 2011, [18F]-FDG PET/CT simulation was performed on 68 consecutive patients with pharyngeal cancers (PET/CT group). As an historical control, conventional CT simulation was performed on 56 consecutive patients with pharyngeal cancer between 2000 and 2006 (CT group). In the PET/CT group, the primary sites were nasopharynx (NPC), oropharynx (OPC), and hypopharynx (HPC) in 35, 20, and 13 patients, respectively; in the CT group, the primary sites were NPC, OPC, and HPC in 21, 17, and 18 patients, respectively. All but five patients in the PET/CT group were treated with intensity modulated radiation therapy (IMRT). RESULTS: In the PET/CT group, TNM and clinical stages changed in 11 (16 %) and eight (12 %) patients, respectively. Although the 5-year overall survival (OS) rates for the PET/CT and the CT groups were 80 and 64 %, respectively (p = 0.0420), this result may be attributable to the background difference between the two groups. Similarly, the 5-year locoregional control rates of the two groups were 82 and 70 %, respectively (p = 0.0501). Notably, marginal recurrences around the planning target volume (PTV) were only noted in four CT group patients. CONCLUSION: PET/CT simulation was useful for delineating an accurate clinical target volume (CTV) of pharyngeal cancer, and its clinical results were satisfactory.

Clinical results of definitive-dose (50 Gy/25 fractions) preoperative chemoradiotherapy for unresectable esophageal cancer.

BACKGROUND: The clinical results of definitive-dose preoperative chemoradiotherapy (CRT) of 50 Gy/25 fractions/5 weeks for unresectable esophageal cancer were analyzed. METHODS: Inclusion criteria were unresectable esophageal squamous cell carcinoma with T4b or mediastinal lymph nodes invading to the trachea or aorta. Radiation therapy of 50 Gy/25 fractions/5 weeks was combined concurrently with two courses of FP therapy (CDDP 70 mg/m(2) + 5-FU 700 mg/m(2)/d × 5 days: day 1-5, day 29-33). Tumor response was evaluated 4 weeks after completion of RT. Subtotal esophagectomy was planned 6-8 weeks after RT. RESULTS: Thirty patients (26 male and 4 female) aged from 50-78 years (median 66) were enrolled between 2008 and 2011. The clinical stages according to the 7th edition of UICC were stages II/III/IV, 1/23/6; T1/2/3/4, 1/1/4/24; and N0/1/2/3, 3/25/1/1. All 30 patients completed RT of 50 Gy/25 fractions. Initial tumor responses were 21 patients with resectable disease, 7 with unresectable disease, and 2 with progressive disease. Subtotal esophagectomy was performed in 18 (60%) of the 30 patients. Pathological complete response was obtained in five (28%) patients. There were two patients with hospitalization death after surgery (11%). Six of the 7 patients who still had unresectable disease were treated with 1-3 courses of docetaxel, CDDP and 5-FU. Three patients treated without surgery showed long-term survival. The 3-year loco-regional control rate and the 3-year overall survival rate for the 30 patients were 70 and 49%, respectively. CONCLUSIONS: Definitive-dose preoperative CRT was feasible, and is a promising treatment strategy for unresectable esophageal cancer.

Efficacy of silodosin in patients undergoing brachytherapy: a randomized trial involving a pressure flow study.

PURPOSE: The purpose of the study is to investigate the efficacy of an alpha-1 adrenergic receptor antagonist (silodosin) for the treatment of lower urinary tract symptoms (LUTS) associated with interstitial (125)I implantation for prostate cancer. METHODS: This randomized single-center study involved 105 patients (53 with and 52 without silodosin). Silodosin was postoperatively administered, daily, for 6 months (8 mg/day). Urinary symptoms and pressure flow were evaluated preoperatively and postoperatively at 1, 3, 6, and 12 months. RESULTS: At 12 months, interstitial (125)I implantation had induced a significant decrease in prostate volume (28.3 ± 11.1-20.5 ± 8.1 g in the silodosin group and 26.1 ± 9.7-17.7 ± 4.9 g in the controls) and the prostate-specific antigen level (7.1 ± 3.6-1.4 ± 1.7 ng/mL in the silodosin group and 8.1 ± 4.3-1.3 ± 1.2 ng/mL in the controls). Significant improvements in the international prostate symptom voiding subscores at 6 months and quality of life at 3 months were observed in those receiving silodosin. The pressure flow studies demonstrated that silodosin had significantly enlarged the bladder capacity when the first non-voiding contraction was seen at 3 and 12 months (3M: 127.1 ± 74.8 vs. 118.2 ± 83.9 mL, p = 0.001; 12M: 123.7 ± 79.3 vs. 100.3 ± 73.4 mL, p = 0.01); however, there were no improvements in the bladder outlet obstruction index (BOOI) or urinary flow. CONCLUSIONS: Silodosin temporarily improved LUTS, but did not improve the BOOI after (125)I implantation in the prostate.

A phase I study of split-dose cisplatin and etoposide with concurrent accelerated hyperfractionated thoracic radiotherapy in elderly patients with limited-disease small cell lung cancer.

OBJECTIVE: The optimal treatment for elderly patients with limited-disease small cell lung cancer has not been defined. We therefore performed a Phase I study for split-dose cisplatin plus etoposide combined with early concurrent accelerated hyperfractionated thoracic radiotherapy in elderly (70 years of age or older) patients with limited-disease small cell lung cancer. METHODS: Chemotherapy consisted of cisplatin at 20 or 25 mg/m(2) and etoposide at 80 mg/m(2), both administered on Days 1-3 of a 28-day cycle. Radiotherapy was initiated at the onset of chemotherapy and administered at a dose of 1.5 Gy twice daily over 3 weeks up to a total dose of 45 Gy. RESULTS: Twelve patients with a median age of 76 years (range, 70-85) were enrolled. Dose-limiting toxicities occurred in two (hyponatremia of Grade 4 or cardiac ischemia of Grade 3) of the six patients treated at dose Level 1 as well as in three (perforation of the sigmoid colon of Grade 3, febrile neutropenia of Grade 3, or hyponatremia of Grade 3) of the six patients treated at dose Level 2. The most frequent non-hematologic adverse events included anorexia, fatigue, esophagitis and pneumonitis, but most of these events were of Grade 1 or 2. CONCLUSIONS: The recommended dose for cisplatin and etoposide chemotherapy administered on Days 1-3 was determined to be 20 and 80 mg/m(2), respectively. Our results indicate that split-dose cisplatin plus etoposide chemotherapy combined with early concurrent accelerated hyperfractionated thoracic radiotherapy is well tolerated by elderly patients with limited-disease small cell lung cancer. CLINICAL TRIALS REGISTRATION NO: UMIN Clinical Trials Registry (UMIN-CTR) C000000143.

Radiation-Induced Lymphopenia and Its Impact on Survival in Patients with Brain Metastasis.

BACKGROUND: Differences in radiation-induced lymphopenia and prognosis between methods of radiotherapy (RT) for brain metastases remain unclear. METHODS: In this retrospective analysis of patients who underwent whole-brain radiotherapy (WBRT) or stereotactic radiosurgery/radiotherapy (SRS/SRT) for brain metastases, baseline total lymphocyte count (TLC) data were obtained within 2 weeks before RT initiation. Follow-up TLC data were evaluated at 0-2, 2-4, and 4-8 weeks after RT completion. Persistent lymphopenia was defined as <800/µL at any time point. RESULTS: Overall, 138 RT courses in 128 patients were eligible (94 WBRT; 44 SRS/SRT). In the WBRT courses, the median baseline TLC was 1325/µL (IQR: 923-1799). Follow-up TLC decreased significantly to 946/µL (626-1316), 992/µL (675-1291), and 1075/µL (762-1435) (p < 0.001). SRS/SRT courses showed no significant TLC decrease. Multivariate analysis revealed female sex, prior RT, baseline TLC < 800/µL, and WBRT use were significantly associated with persistent lymphopenia. In the WBRT group, overall survival was significantly different between those with and without persistent lymphopenia (median, 2.6 and 6.1 months; p < 0.001). However, there was no significant difference in survival in the SRS/SRT group (p = 0.60). CONCLUSION: This study suggests SRS/SRT might be preferable for lymphocyte preservation in brain metastasis patients.

Visualization of tumor hypoxia and re-oxygenation after stereotactic body radiation therapy in early peripheral lung cancer: A prospective study.

BACKGROUND AND PURPOSE: In this study, fluoromisonidazole positron emission tomography (F-MISO PET/CT) was used to evaluate tumor hypoxia and re-oxygenation in patients with lung tumors treated with stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: Patients with T1-2 N0 lung cancer were included in this study. The prescribed dose was 48-52 Gy in four fractions. F-MISO PET/CT was performed twice, before SBRT and 1-3 days after the first irradiation. The maximum standardized uptake value (SUVmax) and tumor/muscle ratio (TMR) were evaluated as indicators of hypoxia. The threshold for hypoxia was defined as a TMR of 1.30 or more. RESULTS: Between 2016 and 2021, 15 patients were included. Pre-treatment tumor hypoxia was observed in nine tumors (60 %). TMR in all six tumors without pre-treatment hypoxia rose after single high-dose irradiation. In contrast, TMR in six of nine tumors with pre-treatment hypoxia dropped after irradiation, suggesting re-oxygenation. Although no local recurrence was noted, regional and/or distant relapses were seen in four patients (27 %). Of these, three had tumors with abnormal F-MISO uptake. The remaining patient had a tumor without signs of hypoxia on pre-treatment PET/CT. The 2-year progression free survival of patients with tumors with and without pre-treatment hypoxia were 30 % and 63 %, respectively (p = 0.319). CONCLUSION: Tumor hypoxia reduced after single high-dose irradiation. Tumor with F-MISO uptake seems to be an unfavorable prognostic factor in lung SBRT.

Impact of rectal gas on the planning target volume margin for pelvic bone and prostate matching in prostate cancer patients receiving volumetric-modulated arc therapy.

We performed daily cone-beam computed tomography (CBCT) to determine the impact of rectal gas on the movements of prostate and seminal vesicles (SVs). We aimed to determine the relationship between planning target volume (PTV) margins and rectal gas. In 30 treatments of 15 prostate cancer patients, excessive rectal gas was removed and CBCT images were analyzed. Image registration between planning CT and daily CBCT images before and after rectal gas removal was performed for pelvic bone and prostate matching. The couch movement distance between each matching was considered the prostate movement. In addition, we measured SV tip movement between each matching. The anterior-posterior movement of the prostate before rectal gas removal (3.1 ± 2.9 mm) was significantly greater than that after rectal gas removal (1.2 ± 1.2 mm; p < 0.01). The left-right and superior-inferior movements were similar regardless of the presence or absence of rectal gas. The SV movement distances before and after rectal gas removal were 11.0 ± 5.8 mm and 4.6 ± 3.8 mm, respectively (p < 0.01), in pelvic bone matching, and 8.0 ± 4.2 mm and 3.8 ± 3.2 mm, respectively (p < 0.01), in prostate matching. After rectal gas removal, the SV position did not differ significantly between each matching. In 26 of the 30 treatments, SV movement distance in the presence of rectal gas was >6 mm, which is the minimum PTV margin at our institution. In comparison, after rectal gas removal and prostate matching, only 6 treatments demonstrated an SV movement distance of >6 mm. In the presence of rectal gas, the SVs require greater PTV margins than the prostate. Rectal gas removal should be considered if the movement distance on prostate matching is greater than the minimum PTV margin at treating institution.

Recurrence patterns and progression-free survival after chemoradiotherapy with or without consolidation durvalumab for stage III non-small cell lung cancer.

Chemoradiotherapy followed by consolidation durvalumab (CCRT+D) improves survival in patients with stage III non-small-cell lung cancer (NSCLC). We compared recurrence patterns and survival in the CCRT+D and CCRT cohorts. We conducted a multicenter, retrospective study in Japan. Patients who received CCRT for stage III NSCLC were included in this study. Of 178 eligible patients, 136 were in the CCRT+D and 42 were in the CCRT cohorts. Locoregional recurrence (LR), LR plus distant metastases (DM), and DM were observed in 20.6%, 8.8%, 27.9% of the CCRT+D, and 26.2%, 16.7% and 33.3% of the CCRT cohorts, respectively. In-field recurrence was the most common LR pattern in both cohorts. Squamous cell carcinoma and PD-L1 expression < 1%, and female sex and EGFR mutations were significantly associated with an increased risk of LR and DM. In patients with any risk factors for LR, the incidence of LR was similar in the CCRT+D and CCRT (39.5% vs 45.5%). The 24 month progression-free survival (PFS) and overall survival (OS) were 40.3% and 69.4% in the CCRT+D and 24.7% and 61.0% in the CCRT cohorts, respectively. Poor performance status and no consolidation durvalumab were significantly associated with shorter PFS. There was a significant difference in PFS between the CCRT+D and CCRT in the propensity score-matched cohort (HR = 0.51, P = 0.005). In conclusion, consolidation durvalumab decreased both LR and DM, and significantly improved PFS. However, in-field recurrence was still a major problem, as well as DM.

Long-term follow-up of a randomized Phase II study of cisplatin/5-FU concurrent chemoradiotherapy for esophageal cancer (KROSG0101/JROSG021).

OBJECTIVE: Long-term survival and late toxicities of a randomized Phase II study of chemoradiotherapy for esophageal cancer were analyzed. METHODS: Eligible patients were <75 years old and performance status 0-2, and had Stages II-IVA esophageal cancer. For arm A (short-term infusion), cisplatin 70 mg/m(2) Days 1 and 29 and 5-fluorouracil 700 mg/m(2) Days 1-5 and 29-33 were given concurrently with radiotherapy of 60 Gy/30 fr/7 weeks (1 week split). For arm B (protracted infusion), cisplatin 7 mg/m(2) Days 1-5, 8-12, 29-33 and 36-40, and 5-fluorouracil 250 mg/m(2) Days 1-14 and 29-42 were given with the same radiotherapy. Two cycles of consolidation cisplatin/5-fluorouracil chemotherapy were given to both arms. RESULTS: Between 2001 and 2006, 91 patients were enrolled; 46 were randomized to arm A, and 45 to arm B. The 2- and 5-year overall survival rates for arm A were 46 and 35% (95% confidence interval: 22-48%), while those for arm B were 44 and 22% (11-35%), respectively. Excluding four patients with early death, seven (17%) patients in arm A and eight (18%) in arm B showed late toxicities of Grade 3 or more. Most of the toxicities were cardiac or pleural toxicities. Patients with severe late toxicities often had coexistent hypothyroidism. There were three patients with a secondary malignancy possibly related to treatment. CONCLUSIONS: Low-dose protracted infusion chemotherapy with radiotherapy is not superior to full-dose short-term infusion chemotherapy with radiotherapy for esophageal cancer. Late toxicities, including cardiac and pleural toxicities, hypothyroidism and secondary malignancy, should be carefully monitored.