Impact of concurrent antibody-drug conjugates and radiotherapy on symptomatic radiation necrosis in breast cancer patients with brain metastases: a multicenter retrospective study.

AIM: We aimed to investigate the impact of concurrent antibody-drug conjugates (ADC) and radiotherapy on symptomatic radiation necrosis (SRN) in breast cancer patients with brain metastases (BM). METHODS: This multicenter retrospective study uses four institutional data. Eligibility criteria were histologically proven breast cancer, diagnosed BM with gadolinium-enhanced MRI, a Karnofsky performance status of 60 or higher, and radiotherapy for all BM lesions between 2017 and 2022. Patients with leptomeningeal dissemination were excluded. Concurrent ADC was defined as using ADC within four weeks before or after radiotherapy. The cumulative incidence of SRN until December 2023 with death as a competing event was compared between the groups with and without concurrent ADC. Multivariable analysis was performed using the Fine-Gray model. RESULTS: Among the 168 patients enrolled, 48 (29%) received ADC, and 19 (11%) had concurrent ADC. Of all, 36% were HER2-positive, 62% had symptomatic BM, and 33% had previous BM radiation histories. In a median follow-up of 31 months, 18 SRNs (11%) were registered (11 in grade 2 and 7 in grade 3). The groups with and without concurrent ADC had 5 SRNs in 19 patients and 13 SRNs in 149, and the two-year cumulative incidence of SRN was 27% vs. 7% (P = 0.014). Concurrent ADC was associated with a higher risk of SRN on multivariable analysis (subdistribution hazard ratio, 3.0 [95% confidence interval: 1.1-8.3], P = 0.030). CONCLUSIONS: This study suggests that concurrent ADC and radiotherapy are associated with a higher risk of SRN in HER2-positive breast cancer patients.

Definitive radiotherapy for nasopharyngeal carcinoma in Japan: analysis of cases in the National Head and Neck Cancer Registry from 2011 to 2014.

OBJECTIVE: This study aimed to analyze the nationwide prognosis of patients with nasopharyngeal carcinoma who underwent definitive radiotherapy in Japan, utilizing the National Head and Neck Cancer Registry data. METHODS: A total of 741 patients diagnosed with primary nasopharyngeal carcinoma were screened from 2011 to 2014. The inclusion criteria were histologically proven nasopharyngeal squamous cell carcinoma, receiving definitive radiotherapy, and no distant metastases. Patients with unclear prognoses or unknown staging were excluded. The primary endpoint was 5-year overall survival, and secondary endpoints were 5-year progression-free survival and survival by stage. RESULTS: A total of 457 patients met the inclusion criteria. The median age was 60 years, and 80% were male. The proportions of patients with performance status 0, 1, 2 and 3 were 69, 10, 1 and 1%, respectively. Chemoradiotherapy was administered to 84.7%. Radiotherapy modalities were recorded only for 29 patients (three received intensity-modulated radiotherapy and 26 received two/three-dimensional radiotherapy). Of those included, 7.4, 24.7, 35.7, 24.5 and 7.7% had Stage I, II, III, IVA and IVB disease, respectively. The 5-year overall survival was 72.5% for all patients: 82.6, 86.6, 76.0, 51.4 and 66.5% for Stage I, II, III, IVA and IVB disease, respectively. The 5-year progression-free survival was 58.6%: 75.6, 66.8, 61.5, 43.7 and 46.5% for Stage I, II, III, IVA and IVB disease, respectively. CONCLUSIONS: This nationwide survey demonstrated favorable prognoses and provided valuable foundational data for similar future surveys to monitor the penetration of appropriate treatment and changes in clinical structures based on new evidence.

Retrospective non-inferiority study of stereotactic radiosurgery for more than ten brain metastases.

AIM: This study aimed to investigate the clinical benefits of stereotactic radiosurgery (SRS) in patients with > 10 brain metastases (BM) compared to patients with 2-10 BM. METHODS: The study included multiple BM patients who underwent SRS between 2014 and 2022, excluding patients who underwent whole brain radiotherapy, had a Karnofsky Performance Status score < 60, suspected leptomeningeal disease, or a single BM lesion. Patients were divided into two groups (2-10 and > 10 BM groups) and matched 2:1 based on propensity scores. The primary endpoint was overall survival (OS) in the matched dataset, with intracranial progression-free survival (PFS) as the secondary endpoint. Non-inferiority was established if the upper limit of the 95% confidence interval (CI) of the adjusted hazard ratio was below 1.3. RESULTS: Of the 1042 patients identified, 434 met eligibility criteria. After propensity score matching, 240 patients were analyzed (160 in the BM 2-10 group and 80 in the > 10 BM group). The median OS was 18.2 months in the 2-10 BM group and 19.4 months in the > 10 BM group (P = 0.60). The adjusted hazard ratio was 0.86 (95% CI: 0.59-1.24), indicating non-inferiority. PFS was not significantly different between the groups (4.8 months vs. 4.8 months, P = 0.94). The number of BM did not significantly impact OS or PFS. CONCLUSIONS: SRS for selected patients with > 10 BM was non-inferior in terms of OS compared to those with 2-10 BM in a propensity score-matched dataset.

Multicenter retrospective study of stereotactic body radiotherapy for patients with previously untreated initial small hepatocellular carcinoma.

AIM: We aimed to verify the therapeutic efficacy and safety of stereotactic body radiotherapy (SBRT) for previously untreated initial small hepatocellular carcinoma (HCC) in a multicenter, retrospective study. METHODS: Patients who underwent SBRT for HCC at the Japanese Society of Clinical Oncology (JCOG) member hospitals in Japan between July 2013 and December 2017 and met the following eligibility criteria were included: (1) initial HCC; (2) ≤3 nodules, ≤5 cm in diameter; (3) Child-Pugh score of A or B; and (4) unsuitability for or refusal of standard treatment. We analyzed the overall survival, recurrence-free survival, and cumulative incidence of local recurrence rate, and adverse events directly related to SBRT. RESULTS: Seventy-three patients with 79 lesions from 14 hospitals were analyzed. The median age was 77 years (range: 50-89 years), and the median tumor size was 23 mm (range: 6-50 mm). The median radiation dose was 40 Gy (range: 35-60 Gy) in five fractions (range: 4-8). The median follow-up period was 45 months (range: 0-103 months). The 3-year overall survival, recurrence-free survival, and cumulative incidence of local recurrence rates were 69.9% (95% CI: 58.7%-81%), 57.9% (95% CI: 45.2%-70.5%), and 20.0% (95% CI: 11.2%-30.5%), respectively. Four cases (5.5%) of adverse events of grade 3 or higher were reported: three cases of grade 3 and one case of grade 4 (duodenal ulcer). No grade 5 toxicities were observed. CONCLUSION: SBRT is a promising treatment modality, particularly for small HCCs, as they are not suitable for standard treatment.

Recent trends of characteristics and treatments in adults with newly diagnosed brain metastases.

OBJECTIVE: We aimed to evaluate recent trends in characteristics and treatments among patients with brain metastases in clinical practice. METHODS: All newly diagnosed patients with brain metastases during 2016-2021 at a single cancer center were enrolled. We collected the detailed features of each patient and estimated the number of candidates considered to meet the following criteria used in common clinical trials: Karnofsky performance status ≥ 70 and mutated non-small cell lung cancer, breast cancer or melanoma. The brain metastases treatments were classified as follows: (i) stereotactic radiosurgery, (ii) stereotactic radiosurgery and systemic therapy, (iii) whole-brain radiotherapy, (iv) whole-brain radiotherapy and systemic therapy, (v) surgery, (vi) immune checkpoint inhibitor or targeted therapy, (vii) cytotoxic agents and (ix) palliative care. Overall survival and intracranial progression-free survival were estimated from brain metastases diagnosis to death or intracranial progression. RESULTS: A total of 800 brain metastases patients were analyzed; 597 (74.6%) underwent radiotherapy, and 422 (52.7%) underwent systemic therapy. In addition, 250 (31.3%) patients were considered candidates for common clinical trials. Compared to 2016, the later years tended to shift from whole-brain radiotherapy to stereotactic radiosurgery (whole-brain radiotherapy: 35.7-29.1% and stereotactic radiosurgery: 33.4-42.8%) and from cytotoxic agents to immune checkpoint inhibitor/targeted therapy (cytotoxic agents: 10.1-5.0 and immune checkpoint inhibitor/targeted therapy: 7.8-10.9%). There was also an increase in the proportion of systemic therapy combined with radiation therapy (from 26.4 to 36.5%). The median overall survival and progression-free survival were 12.7 and 5.3 months, respectively. CONCLUSIONS: This study revealed the diversity of brain metastases patient characteristics, recent changes in treatment selection and the percentage of candidates in clinical trials.

Radiotherapy or systemic therapy versus combined therapy in patients with brain metastases: a propensity-score matched study.

AIM: This study aimed to evaluate the clinical benefits of systemic therapy (ST) combined with stereotactic radiosurgery (SRS) for brain metastases (BM). METHODS: The patient data were extracted from the institutional disease database from 2016 to 2021. Surgical and whole-brain radiotherapy cases and poor Karnofsky performance status (KPS < 70) were excluded. The eligible patients were divided into monotherapy (SRS alone or ST alone) and combined therapy (SRS and ST, combined within a month). Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of death and intracranial progression. The propensity score for selecting treatment was calculated based on existing prognostic covariates. Two groups were matched 1:1 and compared for intracranial progression-free survival (PFS) and overall survival (OS). RESULTS: We identified 1605 patients and analyzed 928 (monotherapy: n = 494, combined therapy: n = 434). In a multivariable model, the combined therapy was independently associated with improved PFS and OS relative to the monotherapy. At the median follow-up of 383 days in the matched dataset, the combined therapy group showed significantly longer PFS (median, 7.4 vs. 5.0 months, P < 0.001) and OS (median, 23.1 vs. 17.2 months, P = 0.036) than the monotherapy group. The overall intracranial progression and mortality risk was reduced in the combined therapy group, with an estimated HR of 0.70 and 0.78. CONCLUSIONS: Combined therapy exhibited longer PFS and OS than monotherapy in BM patients. The results support the recent trend toward combining systemic and local therapies, encouraging future clinical trials.

The importance of choosing the right strategy to treat small cell carcinoma of the cervix: a comparative analysis of treatments.

BACKGROUND: Standard treatments for small cell carcinoma of the cervix (SCCC) have not been established. In this study, we aimed to estimate the optimal treatment strategy for SCCC. METHODS: This was a multicenter retrospective study. Medical records of patients with pathologically proven SCCC treated between 2003 and 2016 were retrospectively analyzed. Overall survival (OS) was plotted using the Kaplan-Meier method. Log-rank tests and Cox regression analysis were used to assess the differences in survival according to stage, treatment strategy, and chemotherapy regimen. RESULTS: Data of 78 patients were collected, and after excluding patients without immunohistopathological staining, 65 patients were evaluated. The median age of the included patients was 47 (range: 24-83) years. The numbers of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stages I-IIA, IIB-IVA, IVB were 23 (35%), 34 (52%), and 8 (12%), respectively. Of 53 patients who had undergone chemotherapy, 35 and 18 received SCCC and non-SCCC regimens as their first-line chemotherapy regimen, respectively. The 5-year OS for all patients was 49%, while for patients with FIGO stages I-IIA, IIB-IVA, IVB, it was 60, 50, and 0%, respectively. The 5-year OS rates for patients who underwent treatment with SCCC versus non-SCCC regimens were 59 and 13% (p < 0.01), respectively. This trend was pronounced in locally advanced stages. Multivariate analysis showed that FIGO IVB at initial diagnosis was a significant prognostic factor in all patients. Among the 53 patients who received chemotherapy, the SCCC regimen was associated with significantly better 5-year OS in both the uni- and multivariate analyses. CONCLUSION: Our results suggest that the application of an SCCC regimen such as EP or IP as first-line chemotherapy for patients with locally advanced SCCC may play a key role in OS. These findings need to be validated in future nationwide, prospective clinical studies.

Examination of the best head tilt angle to reduce the parotid gland dose maintaining a safe level of lens dose in whole-brain radiotherapy using the four-field box technique.

The parotid gland is recognized as a major-risk organ in whole-brain irradiation; however, the beam delivery from the left and right sides cannot reduce the parotid gland dose. The four-field box technique using a head-tilting device has been reported to reduce the parotid gland dose by excluding it from the radiation field. This study aimed to determine the appropriate head tilt angle to reduce the parotid gland dose in the four-field box technique. The bilateral, anterior, and posterior beams were set for each of ten patients. The orbitomeatal plane angle (OMPA) was introduced as an indicator that expresses the head tilt angle. Next, principal component analysis (PCA) was performed to understand the interrelationship between variables (dosimetric parameters of the lens and parotid gland and OMPA). In PCA, the angle between the OMPA vector and maximum lens dose or mean parotid gland dose vector was approximately opposite or close, indicating a negative or positive correlation [r = -0.627 (p < 0.05) or 0.475 (p < 0.05), respectively]. The OMPA that reduced the maximum lens dose to <10 Gy with a 95% confidence interval was approximately 14°. If the lens dose was not considered, the parotid gland dose could be reduced by decreasing the OMPA.

Role of high-dose salvage radiotherapy for oligometastases of the localised abdominal/pelvic lymph nodes: a retrospective study.

BACKGROUND: Abdominal/pelvic lymph node (LN) oligometastasis, a pattern of treatment failure, is observed occasionally, and radiotherapy may work as salvage therapy. The optimal prescription dose, however, is yet to be determined. This study assessed the efficacy of high-dose radiotherapy. METHODS: The medical records of 113 patients at 4 institutes were retrospectively analysed who had 1 to 5 abdominal/pelvic LN oligometastases and were treated with definitive radiotherapy between 2008 and 2018. The exclusion criteria included non-epithelial tumours, uncontrolled primary lesions, palliative intent, and re-irradiation. The prescription dose was evaluated by using the equivalent dose in 2 Gy fractions (EQD2). Patients receiving EQD2 ≥ 60 Gy were placed into the high-dose group, and the remaining others the low-dose group. Kaplan-Meier analyses were performed to evaluate overall survival (OS), local control (LC), and progression-free survival (PFS). Univariate log-rank and multivariate Cox proportional hazards model analyses were performed to explore predictive factors. Adverse events were compared between the high-dose and low-dose groups. RESULTS: The primary tumour sites included the colorectum (n = 28), uterine cervix (n = 27), endometrium (n = 15), and ovaries (n = 10). The rate of 2-year OS was 63.1%, that of LC 59.7%, and that of PFS 19.4%. On multivariate analyses, OS were significantly associated with solitary oligometastasis (hazard ratio [HR]: 0.48, p = 0.02), LC with high-dose radiotherapy (HR: 0.93, p < 0.001), and PFS with long disease-free interval (HR: 0.59, p = 0.01). Whereas high-dose radiotherapy did not significantly improve 2-year OS in the entire cohort (74.8% in the high-dose vs. 52.7% in the low-dose; p = 0.08), it did in the subgroup of solitary oligometastasis (88.8% in the high-dose vs. 56.3% in the low-dose; p = 0.009). As for Late grade ≥ 3 adverse event, ileus was observed in 7 patients (6%) and gastrointestinal bleeding in 4 (4%). No significant association between the irradiation dose and adverse event incidence was found. CONCLUSIONS: As salvage therapy, high-dose radiotherapy was recommendable for oligometastasis in the abdominal/pelvic LNs. For solitary oligometastasis, LC and OS were significantly better in the high-dose group.

Impact of treatment planning using a structure block function on the target and organ doses related to patient movement in cervical esophageal cancer: A phantom study.

Helical tomotherapy (HT) can restrict beamlets passing through the virtual contour on computed tomography (CT) image in dose optimization, reducing the dose to organs at risk (OARs). Beamlet restriction limits the incident beamlet angles; thus, the proper planning target volume (PTV) margin may differ from that of the standard treatment plan without beamlet restriction, depending on the patient's movement during dose delivery. Dose distribution changes resulting from patient movement have not been described for treatment plans with beamlet restriction. This study quantified changes in dose distribution to the target and OARs when beamlet restriction is applied to cervical esophageal cancer treatment plan using HT by systematically shifting a phantom. Treatment plans for cervical esophageal cancers with and without beamlet restriction modes [directional block (DB) and nonblock (NB), respectively] were designed for CT images of the RANDO phantom. The PTV margin for the DB mode was set to be the same as that for the NB mode (5 mm). The CT image was intentionally shifted by ±1, ±2, and ±3 voxels in the left-right, anterior-posterior, and superior-inferior directions, and the dose distribution was recalculated for each position using the fluence for the NB or DB mode. When the phantom shift was within the same PTV margin as the NB mode, changes in doses to the targets, lungs, heart, and spinal cord in the DB mode were small as those in the NB mode. In conclusion, the virtual contour shape used in this study would provide safe delivery even with patient movement within the same PTV margin as for the NB mode.

Gross tumor volume in sinonasal tract cancer as a predictor of local recurrence after chemoradiotherapy.

OBJECTIVE: This study investigated whether gross tumor volume of the primary tumor before treatment was a predictor for local recurrence in patients with resectable sinonasal tract squamous cell carcinoma who were treated by chemoradiotherapy. METHODS: A total of 24 patients were enrolled. Pretreatment gross tumor volume of primary tumor was assessed by palpitation, perception and imaging. The cut-off value of the gross tumor volume for local recurrence was determined by receiver-operating curve analysis. A log-rank test and Cox's proportional hazards model were used for univariate and multivariate analyses with adjustment for the clinical T category (cT1-T4a/cT4b), respectively. RESULTS: In the univariate analysis, patients with the gross tumor volume ≥83.7 ml were significantly associated with shorter local recurrence-free rate (P = 0.0023) and disease-free survival (P = 0.0064) than those with gross tumor volume <83.7 ml. In the multivariate analysis, gross tumor volume ≥83.7 ml were significantly associated with shorter local recurrence-free rate (P = 0.041). CONCLUSIONS: Pretreatment gross tumor volume of primary tumor ≥83.7 ml was significantly associated with local recurrence-free rate in resectable sinonasal tract squamous cell carcinoma.

Comparisons of the clinical outcomes of different postoperative radiation strategies for treatment of head and neck squamous cell carcinoma.

PURPOSE: We previously reported unfavorable locoregional control with limited field postoperative radiotherapy for head and neck squamous cell carcinoma patients and thus revised the strategy to cover the whole neck. Head and neck squamous cell carcinoma Patients' outcomes were retrospectively analyzed to compare the efficacy of two treatments. MATERIAL AND METHODS: Before 2010, the clinical target volume covered the tumor bed and/or involved the neck region. Since 2011, whole-neck irradiation was planned. Univariate analysis, multivariate analysis, and propensity score matching were performed. The study included 275 patients: 186 received limited field postoperative radiotherapy and 89 received whole-neck postoperative radiotherapy. The median follow-up time for the entire cohort was 40.8 months. RESULTS: In univariate analysis, the radiation strategy had no significant effect on overall survival and progression-free survival. In multivariate analysis, whole-neck postoperative radiotherapy was a favorable factor for overall survival, progression-free survival, and locoregional control. Propensity score matching resulted in a cohort comprising 118 well-matched patients evenly divided between the limited field postoperative radiotherapy and whole-neck postoperative radiotherapy groups. Whole-neck postoperative radiotherapy group achieved a significantly better 2-year overall survival (56.4% vs. 78.1%; P = 0.003), 2-year progression-free survival (34.7% vs. 59.8%; P = 0.009), and 2-year locoregional control (54.4% vs. 83.2%; P < 0.001). The limited field postoperative radiotherapy group developed significantly more locoregional recurrences both in-field (35.2% vs. 15.1%, P = 0.003) and out-of-field (25.0% vs. 0%, P < 0.001) in the matched-pair cohort. CONCLUSION: Whole-neck postoperative radiotherapy is a more appropriate choice than limited field postoperative radiotherapy to improve overall survival, progression-free survival and locoregional control.

Clinical outcome of definitive radiation therapy for superficial esophageal cancer.

OBJECTIVE: To analyze the clinical outcome of concurrent chemoradiotherapy in superficial esophageal cancer patients. METHODS: We retrospectively analyzed data for 123 patients with superficial esophageal cancer who received external beam radiotherapy without intracavitary brachytherapy plus systemic chemotherapy during 1998-2015. Elective nodal irradiation was not performed. The dosage to planning treatment volume was 60 Gy in 30 fractions. The main outcome measure was overall survival. RESULTS: Patient characteristics were as follows: median age, 66 (41-83) years; male/female ratio, 106/17; squamous cell carcinoma/other, 122/1; cT1a/cT1b, 27/96; cervical esophagus/upper thoracic esophagus/middle thoracic esophagus/lower thoracic esophagus, 7/9/66/41 and concurrent chemoradiotherapy/radiotherapy alone, 100/23. Cisplatin and 5-fluorouracil were the most commonly used agents (85%). At the last follow-up (median 60.5 months), 91 (74%) patients were alive. Complete response was achieved in 116 (94.4%) patients. The 5-year overall survival, progression-free survival and local control rates were 77.0, 46.9 and 62.7%, respectively, similar to that in the elderly patients (P = 0.878, 0.754 and 0.648, respectively). There were 55 failures: 42 local, 10 regional and 3 distant failures. Nine local and seven regional failures developed out-of-field. Thirty-eight local failures (90%) were successfully salvaged, of which 30 (71%) were salvaged via endoscopic removal; only 2 regional failures (20%) were salvaged. Fifteen G3 acute toxicities occurred. One pneumonitis (G3), one pneumothorax (G3) and two pericardial effusion (G2) were the late toxicities observed. There were no G4 toxicities or treatment-related deaths. CONCLUSIONS: Concurrent chemoradiotherapy without intracavitary brachytherapy was effective and safe for superficial esophageal cancer, even in elderly patients.

Trends and distribution of external radiation therapy facilities in Japan based on Survey of Medical Institutions from the Ministry of Health, Labour and Welfare.

This study aimed to explore the distribution of external radiation therapy (RT) facilities, the status of related device installations and the adoption of high-precision RT using Survey of Medical Institutions from the Ministry of Health, Labour and Welfare in Japan. Analysis, categorized by the hospital size and prefecture, provides specific insights into the trends in treatment facility healthcare capabilities. Data on the number of RT facilities, high-precision RT facilities, RT devices and treatment planning systems (TPS) categorized by the number of beds and prefecture from 1996 to 2020 were analyzed. In addition, the study examined the correlation between the high-precision implementation rate and the number of TPSs or radiation oncologists and other medical staff. High-precision RT exceeded 95% in large facilities (800+ beds) but remained <50% in medium-sized facilities (300-499 beds). In a prefecture-by-prefecture analysis, calculation of the maximum-minimum ratio of RT facilities per million population and per 30 km2 revealed a disparity of 3.7 and 73.1 times in the population ratio and the density ratio, respectively. Although a correlation was found between the number of TPSs per RT device or the number of medical physicists per million population and the rate of high-precision RT implementation, no correlation was found among other professions. Detailed analysis based on the hospital size and prefecture provided more specific information on the medical functions of RT facilities in Japan. These findings can potentially contribute to the future development of RT, including the standardization of treatment techniques and optimal resource allocation.

Changing trends in gamma knife surgery to linear accelerator brain stereotactic radiotherapy in Japan: a survey based on the nationwide claims database.

PURPOSE: This study evaluated the trends in the platform for stereotactic radiotherapy to the brain (SRT), utilizing the open data of the National Database published by the Ministry of Health, Labour, and Welfare. MATERIALS AND METHODS: This study analyzed data from FY2014 to FY2021. The practices included in the study were gamma knife surgery (GKS) and SRT with a linear accelerator (LINAC). The total number of outpatient and inpatient cases in each SRT system was evaluated annually. RESULTS: From April 2014 to March 2022, the study included 212,016 cases (102,691 GKS and 109,325 LINAC) of the registered 1,996,540 radiotherapy cases. In the first year, 13,117 (54.1%) cases were GKS, and 11,128 (45.9%) were LINAC; after that, GKS decreased, and LINAC increased, reaching the same rate in FY2017. Compared to the first year, the final year showed 11,702 GKS (- 1415 or - 10.8%) and 17,169 LINAC (+ 6041 or + 54.3%), with an increase of 4626 total SRT cases to 28,871 (+ 19.1%). The percentage of outpatient treatment also increased from 4.6 to 11.8% for GKS and from 44.7 to 57.9% for LINAC. CONCLUSION: The study found a gradual decrease in the selection of GKS, an increasing trend in the selection of LINAC, and an increase in the overall number of stereotactic irradiations. In particular, the proportion of outpatient treatment increased, indicating that more than half of LINAC was selected for outpatient treatment.

Palliative radiotherapy for painful non-bone lesions in patients with advanced cancer: a single center retrospective study.

PURPOSE: This retrospective study aimed to assess the efficacy and safety of palliative radiotherapy for painful non-bone lesions in patients with advanced cancer. MATERIALS AND METHODS: We enrolled patients with painful non-bone lesions who underwent conventional palliative radiotherapy between September 2018 and September 2022. The treatment targets included primary tumor lesions, lymph node metastases, non-bone hematogenous metastases, and other lesions. The primary endpoint was the overall pain response rate in evaluable patients, determined based on the International Consensus Pain Response Endpoint criteria. The secondary endpoints included overall survival, pain recurrence, and adverse events. RESULTS: Of the 420 screened patients, 142 received palliative radiotherapy for painful non-bone lesions, and 112 were evaluable. A pain response was achieved in 67 patients (60%) of the 112 evaluable patients within a median of 1.2 months. Among these patients, 25 exhibited complete response, 42 partial response, 18 indeterminate response, and 27 pain progression. The median survival time was 5.5 months, recorded at a median follow-up of 6.0 months, during which 67 patients died. Multivariate analysis identified poor performance status scores of 2-4, opioid use, and re-irradiation as independent factors associated with a reduced likelihood of achieving a pain response. Pain recurrence occurred in 18 patients over a median of 4.1 months. Seventeen patients had grade 1-2 adverse events, while none experienced grade 3 or higher toxicity. CONCLUSION: Palliative radiotherapy can potentially be a safe and well-tolerated modality for managing painful non-bone lesions, with a low rate of adverse events.

Re-irradiation spine stereotactic body radiotherapy following high-dose conventional radiotherapy for metastatic epidural spinal cord compression: a retrospective study.

PURPOSE:  We aimed to evaluate the efficacy and safety of re-irradiation stereotactic body radiation therapy (SBRT) in patients with metastatic epidural spinal cord compression (MESCC) following high-dose conventional radiotherapy. MATERIALS AND METHODS:  Twenty-one patients met the following eligibility criteria: with an irradiation history of 50 Gy2 equivalent dose in 2-Gy fractions (EQD2) or more, diagnosed MESCC in the cervical or thoracic spines, and treated with re-irradiation SBRT of 24 Gy in 2 fractions between April 2018 and March 2023. Prior treatment was radiotherapy alone, not including surgery. The primary endpoint was a 1-year local failure rate. Overall survival (OS) and treatment-related adverse events were assessed as the secondary endpoints. Since our cohort includes one treatment-related death (TRD) of esophageal perforation, the cumulative esophageal dose was evaluated to find the dose constraints related to severe toxicities. RESULTS:  The median age was 68, and 14 males were included. The primary tumor sites (esophagus/lung/head and neck/others) were 6/6/7/2, and the median initial radiotherapy dose was 60 Gy2 EQD2 (range: 50-105 Gy2, 60-70/ > 70 Gy2 were 11/4). Ten patients underwent surgery followed by SBRT and 11 SBRT alone. At the median follow-up time of 10.4 months, 17 patients died of systemic disease progression including one TRD. No radiation-induced myelopathy or nerve root injuries occurred. Local failure occurred in six patients, with a 1-year local failure rate of 29.3% and a 1-year OS of 55.0%. Other toxicities included five cases of vertebral compression fractures (23.8%) and one radiation pneumonitis. The cumulative esophageal dose was recommended as follows: Dmax < 203, D0.035 cc < 187, and D1cc < 167 (Gy3 in biological effective dose). CONCLUSION:  Re-irradiation spine SBRT may be effective for selected patients with cervical or thoracic MESCC, even with high-dose irradiation histories. The cumulative dose assessment across the original and re-irradiated esophagus was recommended to decrease the risk of severe esophageal toxicities.

Classification of Patients With Painful Tumors to Predict Response to Palliative Radiation Therapy.

PURPOSE: This study aimed to identify factors affecting pain response to develop a patient classification system for palliative radiation therapy (RT). METHODS AND MATERIALS: Our prospective observational study (UMIN000044984) provided data on patients who received palliative RT for painful tumors. The eligibility criteria were having a numerical rating scale (NRS) score of 2 or more before treatment and receiving palliative RT between August 2021 and September 2022. Post-RT follow-up was scheduled prospectively at 2, 4, 12, 24, 36, and 52 weeks. Pain response was assessed using the International Consensus Pain Response Endpoints criteria, with the primary outcome being the response rate within 12 weeks. Multivariable logistic regression was performed to identify factors affecting pain response and develop the classification system. Each class evaluated the differences in response rate, time to response, and progression. RESULTS: Of the 488 registered lesions, 366 from 261 patients met the criteria. Most patients had bone metastases (75%), of whom 72% were using opioids and 22% underwent reirradiation. Conventional RT (eg, 8-Gy single fraction, 20 Gy in 5 fractions) was administered to 93% of patients. Over a median of 6.8 months of follow-up, the average NRS decreased from 6.1 to 3.4 at 12 weeks for 273 evaluable lesions, with a 60% response rate. Opioid use and reirradiation negatively affected the response rate in multivariate analysis (P < .01). Lesions were categorized into class 1 (no opioid use and no reirradiation; 89 lesions), class 2 (neither class 1 nor 3; 211 lesions), and class 3 (opioid use and reirradiation; 66 lesions), with respective response rates of 75%, 61%, and 36% (P < .001). Time to response was similar across the classes (P = .91), but the progression rates at 24 weeks differed (11%, 27%, and 63%, respectively; P < .001). CONCLUSIONS: Opioid use and reirradiation are factors leading to significant variations in pain response rates and time to progression.

Deep Learning-based Lung dose Prediction Using Chest X-ray Images in Non-small Cell Lung Cancer Radiotherapy.

Purpose: This study aimed to develop a deep learning model for the prediction of V20 (the volume of the lung parenchyma that received ≥20 Gy) during intensity-modulated radiation therapy using chest X-ray images. Methods: The study utilized 91 chest X-ray images of patients with lung cancer acquired routinely during the admission workup. The prescription dose for the planning target volume was 60 Gy in 30 fractions. A convolutional neural network-based regression model was developed to predict V20. To evaluate model performance, the coefficient of determination (R2), root mean square error (RMSE), and mean absolute error (MAE) were calculated with conducting a four-fold cross-validation method. The patient characteristics of the eligible data were treatment period (2018-2022) and V20 (19.3%; 4.9%-30.7%). Results: The predictive results of the developed model for V20 were 0.16, 5.4%, and 4.5% for the R2, RMSE, and MAE, respectively. The median error was -1.8% (range, -13.0% to 9.2%). The Pearson correlation coefficient between the calculated and predicted V20 values was 0.40. As a binary classifier with V20 <20%, the model showed a sensitivity of 75.0%, specificity of 82.6%, diagnostic accuracy of 80.6%, and area under the receiver operator characteristic curve of 0.79. Conclusions: The proposed deep learning chest X-ray model can predict V20 and play an important role in the early determination of patient treatment strategies.

Safety and Efficacy of Gemcitabine Plus Cisplatin Against Recurrent/Metastatic Nasopharyngeal Carcinoma: A Retrospective Study.

BACKGROUND/AIM: Although gemcitabine plus cisplatin (GC) prolongs survival in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) compared with fluorouracil plus cisplatin, no study has evaluated the efficacy and safety of GC in nonendemic regions, including Japan, yet. Therefore, we assessed the safety and efficacy of GC in Japanese patients with R/M NPC. PATIENTS AND METHODS: We retrospectively reviewed patients with R/M NPC who received GC treatment at the Aichi Cancer Center Hospital from January 2017 to March 2020. The main eligibility criteria were histologically confirmed NPC, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2, and locally recurrent disease unsuitable for local treatment or metastatic disease. The regimen was administered every 3 weeks (gemcitabine, 1,000 mg/m2 on days 1 and 8; cisplatin, 80 mg/m2 on day 1). RESULTS: Fourteen patients (median age, 58 years) were included in the study. Two patients had an ECOG PS of 2 and 11 exhibited nonkeratinizing histology. Of the eight patients with measurable lesions, one exhibited complete response and seven exhibited partial response, with an objective response rate of 75%. Median progression-free survival and overall survival were 7.7 and 24.2 months, respectively. Common grade 3 or 4 adverse events included neutropenia (64%), thrombocytopenia (14%), and febrile neutropenia (14%). The median relative dose intensity of gemcitabine and cisplatin was 62% and 60%, respectively. No treatment-related deaths occurred. CONCLUSION: The GC regimen demonstrates promising activity and is tolerable in Japanese patients with R/M NPC.