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.

[Polatuzumab vedotin, bendamustine, and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma, including the outcome as a bridging treatment to CAR-T cell therapy or allogeneic hematopoietic stem cell transplant].

Pola-BR (polatuzumab vedotin, bendamustine, and rituximab) therapy received approval for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in Japan in March 2021. There have been few reports on the efficacy and safety of Pola-BR therapy in Japanese clinical practice. A retrospective analysis was performed on twenty-nine patients with R/R DLBCL who received Pola-BR therapy at our institution (intent to cellular immunotherapy cohort: 20 patients, stand-alone treatment cohort: nine patients). The overall response rate was 69.0% (complete response 27.6%). The median progression-free survival was 5.1 months, with a 9.5-month median overall survival. In the intent to cellular immunotherapy cohort, 11 of 19 patients received chimeric antigen receptor T-cell (CAR-T) infusions, and one patient received allogeneic stem cell transplantation. Four patients received Pola-BR therapy, including bendamustine before leukapheresis, and all produced CAR-T products successfully. 3 of the 28 patients experienced grade3 or higher adverse events, and two required treatment discontinuation. Our single institution, a real-world cohort of R/R DLBCL patients showed high efficacy outcomes and a tolerable toxicity profile for Pola-BR therapy, which is comparable to previous studies. More cases are needed to determine its impact on CAR-T therapy and stem cell transplantation.

Palliative radiotherapy for multiple liver metastases: a retrospective analysis of 73 cases.

BACKGROUND: Whole-liver radiotherapy for diffuse liver metastases can improve symptoms and abnormal liver-related blood data. However, whole-liver radiotherapy is uncommonly used in clinical practice in Japan. Therefore, we aimed to clarify palliative radiotherapy outcomes in Japanese patients with liver metastases. METHODS: We retrospectively reviewed databases in our institution to identify patients treated with radiotherapy (8 Gy in a single fraction) for multiple liver metastases between December 2014 and April 2021. The endpoints included pain response, liver-related blood data and adverse effects. We investigated aspartate transaminase, alanine transaminase, lactate dehydrogenase, alkaline phosphatase, γ-glutamyl transpeptidase and albumin. The mean values at whole-liver radiotherapy and after 2-4 weeks were compared using the Wilcoxon rank-sum test. RESULTS: A total of 73 cases in 71 patients were included. The median clinical target volume was 2118 ml (range, 133-7867 ml). Fifty-seven patients (78%) had finished aggressive treatment at the time of radiotherapy. The median follow-up period was 6 weeks. The pain response rate was 64% (18/28). The mean values of five parameters significantly improved 2-4 weeks after radiotherapy compared to those at baseline: aspartate transaminase (118 vs. 83 U/l P < 0.01); alanine transaminase (84 vs. 61 U/l P < 0.01); lactate dehydrogenase (1351 vs. 1007 U/l P = 0.027); alkaline phosphatase (1624 vs. 1216 U/l P < 0.01) and γ-glutamyl transpeptidase (663 vs. 450 U/l P = 0.037). No patients experienced radiation-induced liver disease. CONCLUSIONS: Palliative radiotherapy is efficient and safe in Japanese patients with liver metastases. These findings will help encourage whole-liver radiotherapy use in Japan.

[Tisagenlecleucel for relapsed/refractory diffuse large B-cell lymphoma: real-world data from single institute experience].

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the approach to patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). This study retrospectively analyzed patients treated with commercially available tisagenlecleucel at our hospital and evaluated its safety and effectiveness. Of the 21 patients evaluated, any grade and grade ≥3 cytokine release syndrome (CRS) occurred in 85.7% and 9.5% of the patients, respectively. A total of 66.7% received tocilizumab and 28.6% received glucocorticoids for the treatment of CRS. The complete response (CR) rate at 3 months was 61.9% (95% confidence interval [CI] 38.4-81.9). After a median follow-up of 6.3 months following CAR-T infusion, the progression-free survival (PFS) and overall survival rates at 6 months were 53.1% (95%CI 28.3-72.7) and 69.2% (95%CI 43.7-84.9), respectively. Severe cytopenia and hypogammaglobulinemia occurred frequently following CAR-T infusion. Eight patients (38.1%) had comorbidities that would have made them ineligible for leukapheresis in the JULIET trial. However, the presence of comorbidities at the time of leukapheresis had no significant effect on the rates of CR, PFS, and adverse events. Tisagenlecleucel for r/r DLBCL in the real-world setting showed high efficacy and manageable safety profile comparable with the pivotal trial.

Radiation therapy and the risk of herpes zoster in patients with cancer.

BACKGROUND: The role and impact of radiation therapy (RT) on the development of herpes zoster (HZ) has not been well studied. The objective of this study was to investigate the association between RT and HZ. METHODS: A propensity score-matched, retrospective cohort study was conducted using institutional cancer registry data and medical records from 2011 to 2015. The risk of developing HZ in the RT and non-RT groups was compared using a Cox proportional hazards model. Associations also were explored between the RT field and the anatomic location of HZ in patients who developed HZ after RT. The expected number of HZ events within the radiation field was calculated according to the RT received by each patient; then, this number was compared with the observed number of in-field events. RESULTS: Of 17,655 patients, propensity score matching yielded 4350 pairs; of these, 3891 pairs were eligible for comparison. The cumulative incidence of HZ in the RT group (vs the non-RT group) during the first 5 years after the index date was 2.1% (vs 0.7%) at 1 year, 3.0% (vs 1.0%) at 2 years, 3.4% (vs 1.3%) at 3 years, 4.1% vs 1.7% at 4 years, and 4.4% vs 1.8% at 5 years. The RT group showed a significantly higher risk of HZ than the non-RT group (hazard ratio, 2.59, 95% CI, 1.84-3.66). In the 120 patients who developed HZ after RT, HZ events were observed significantly more frequently within the RT field than expected (74 vs 43.8 events; P < .001). CONCLUSIONS: Patients with cancer who received RT showed a significantly higher risk of HZ, which was commonly observed within the radiation field.

Postradiotherapy persistent lymphopenia as a poor prognostic factor in patients with cervical cancer receiving radiotherapy: a single-center, retrospective study.

BACKGROUND: Radiotherapy (RT) is effective in cervical cancer; radiation-induced lymphopenia correlates with poor survival outcome in several cancer types. We investigated the association of total lymphocyte count (TLC) with survival outcomes in patients with cervical cancer. METHODS: We retrospectively reviewed 168 patients with cervical cancer initially treated with definitive RT. We obtained clinicopathological data and TLCs before RT and at the end and at 6 months after RT. Patient-, treatment-, and tumor-specific factors were evaluated to determine their predictive values for overall survival. The association of overall and progression-free survivals with lymphopenia at each point was evaluated. RESULTS: Median follow-up duration was 44 (interquartile range: 25-67) months. Median TLCs before RT and at the end and at 6 months after RT were 1625/mm3, 400/mm3, and 800/mm3 (interquartile range: 1270-1930/mm3, 290-550/mm3, and 600-1067/mm3), respectively. For overall survival, in addition to FIGO stage, body mass index, histology, treatment, and presence of para-aortic lymph node metastasis, lymphopenia at 6 months after RT was a poor prognostic factor in multivariate analysis (P = 0.0026; hazard ratio [HR], 3.06; 95% confidence interval [CI]: 1.48-6.33). For progression-free survival, TLCs before and at 6 months after RT were poor prognostic factors in univariate analysis (P = 0.0318 and 0.0081, respectively); however, the latter was the only independent prognostic factor in multivariate analysis (P = 0.0021; HR, 2.67; 95% CI: 1.43-4.99). CONCLUSION: Post-RT persistent lymphopenia could be a poor prognostic factor for patients with cervical cancer who receive RT.

Appropriate endpoints for stereotactic body radiotherapy for bone metastasis: Classification into five treatment groups.

Treatment of bone metastasis using stereotactic body radiotherapy (SBRT) is being widely used in clinical practice. The reported clinical advantages of SBRT include high pain and local control rates, high response rates against bone metastasis from radio-resistant tumors, and safe re-irradiations. Although most reports in the literature use local control as the primary treatment endpoint, this endpoint is not appropriate because local control does not relate directly to patient benefit. Herein, we proposed five pathophysiology-based patient groups, as well as appropriate endpoints for each group.

Clinical outcomes following conventional external beam radiotherapy boost in Japanese patients with cervical cancer who are ineligible for intracavitary brachytherapy.

OBJECTIVE: While external beam radiotherapy boost has been one of the standard management options for locally advanced cervical cancer that is not treatable with intracavitary brachytherapy, its efficacy remains unclear. We assessed clinical outcomes in Japanese patients with cervical cancer who underwent external beam radiotherapy alone and identified related prognostic factors. METHODS: Patients treated with definitive external beam radiotherapy for cervical cancer unsuitable for intracavitary brachytherapy, including whole pelvic irradiation and external beam radiotherapy boost, were retrospectively examined. The endpoints were progression-free survival, overall survival and adverse events. Additionally, various patient-, tumor- and treatment-specific factors were evaluated to identify significant predictors of progression-free survival. RESULTS: The study included 37 patients; 3 (8%), 5 (14%), 17 (46%) and 12 (32%) had clinical International Federation of Gynecology and Obstetrics (FIGO) stages I, II, III and IVA, respectively. A total radiation dose of 56-70.2 Gy was administered (84% of patients received 59.4-60.4 Gy). The median follow-up period after radiotherapy was 17 (range, 2-84) months. The progression-free survival rates at 1 and 2 years were 45 and 29%, respectively; the corresponding overall survival rates were 74 and 43%, respectively. On univariate and multivariate analyses of progression-free survival at 2 years, International Federation of Gynecology and Obstetrics stage IVA and a maximum primary tumor diameter >5 cm were associated with significantly worse outcomes (P = 0.026 and P = 0.027, respectively). CONCLUSION: Approximately 70% of patients with cervical cancer treated with external beam radiotherapy boost instead of intracavitary brachytherapy experienced disease progression within 2 years. These results stress the necessity of devising alternative non-intracavitary brachytherapy treatment approaches, particularly for patients with International Federation of Gynecology and Obstetrics stage IVA and bulky primary tumors.

Determining the recommended dose of stereotactic body radiotherapy boost in patients with cervical cancer who are unsuitable for intracavitary brachytherapy: a phase I dose-escalation study.

OBJECTIVE: Some patients are ineligible for intracavitary brachytherapy (ICBT) for locally advanced cervical cancer. Stereotactic body radiotherapy (SBRT) could be a good treatment option for such patients. This phase I clinical trial aimed to determine the recommended SBRT boost dose for ICBT-ineligible cervical cancer patients. METHODS: Patients with untreated uterine cervical cancer (clinical stages IB1-IIIB) who were ineligible for ICBT were enrolled. Radiotherapy consisted of whole-pelvis radiotherapy (45 Gy in 25 fractions) followed by SBRT. Three dose levels of SBRT (19.5/21/22.5 Gy in three fractions) were set; the treatment protocol began at 21 Gy (level 2). The 'rolling-six' design study was used to establish the recommended dose of SBRT. Each dose level covered three or six patients. The primary endpoint included dose-limiting toxicity (DLT), defined as the occurrence of grade 3 (or worse) non-hematologic adverse effects within 6 months after SBRT. RESULTS: The median follow-up after registration was 17 (range, 8-32) months. Three patients were enrolled in study level 2 (SBRT of 21 Gy); none of the patients exhibited DLT within 6 months after treatment completion. In study level 3 (SBRT of 22.5 Gy), three patients did not exhibit DLT. Although all six patients achieved locoregional control during follow-up, one patient treated with level 2 SBRT experienced distant metastases 14 months after registration. CONCLUSIONS: The recommended dose of SBRT boost was 22.5 Gy in three fractions. We plan to conduct a phase II multi-center clinical trial using the methodology obtained from the current study.

A low albumin to globulin ratio with a high serum globulin level is a prognostic marker for poor survival in cervical cancer patients treated with radiation based therapy.

OBJECTIVE: We investigated whether the pretreatment albumin to globulin ratio, serum albumin level, and serum globulin level can be used to predict survival among cervical cancer patients treated with radiation based therapy and assessed globulin fractions. METHODS: We retrospectively enrolled 128 patients with cervical cancer treated with radiation based therapy at our institution between 2010 and 2015. The associations of the pretreatment albumin to globulin ratio, and serum albumin and globulin levels with overall survival were assessed. Additionally, the associations of the globulin fractions with the serum globulin levels and overall survival were evaluated. RESULTS: Median follow-up duration was 30 months (IQR 16-44 months). A low albumin to globulin ratio (< 1.53) was found to be an independent prognostic factor for overall survival (HR= 3.07; 95% CI, 1.03 to 13.3; P=0.044). On evaluating serum globulin and albumin separately, a high serum globulin level was significantly associated with overall survival (cut-off value 2.9 g/dL; HR=3.74; 95% CI 1.08 to 23.6; P=0.036) whereas a low serum albumin level was not associated with overall survival (cut-off value 3.6 g/dL; HR=1.77; 95% CI 0.57 to 4.54; P=0.29). Electrophoresis data of the serum proteins revealed that the γ-globulin fraction was most strongly correlated with the globulin levels (P<0.001). Furthermore, a high γ-globulin level (≥1.28 g/dL) was significantly associated with poor overall survival (log rank test, P=0.034). CONCLUSIONS: A pretreatment low albumin to globulin ratio, which might be attributable to a high serum globulin level, can be used to predict poor prognosis in cervical cancer patients treated with radiation based therapy.

Re-irradiation for painful bone metastases using stereotactic body radiotherapy.

PURPOSE: Stereotactic body radiotherapy (SBRT) is expected to achieve safe and effective re-irradiation for painful bone metastases. This study aimed to clarify the efficacy of re-irradiation using SBRT for painful bone metastases. METHODS: Prospective database at our institution for the period between September 2013 and December 2017 were retrospectively reviewed for patients with: (1) painful bone metastases; (2) history of radiotherapy to the metastasis; and (3) SBRT performed as re-irradiation. Pain response, pain failure-free duration, analgesics medications, and adverse events were evaluated. Pain was evaluated using the Numerical Rating Pain Score, and pain response was evaluated based on International Consensus Pain Response Endpoints. Best response during follow-up was noted. Patients with complete or partial response were defined as showing pain response, and patients with pain progression were defined as showing pain failure. Adverse events were evaluated based on the RTOG/EORTC Late Radiation Morbidity Scoring Schema. RESULTS: Sixty-six patients selected from our database showed: median age, 65 years (range, 33-82 years); ECOG performance status, 0-1/2/3/4, 51/10/3/2; lesion histopathology, rectal/lung/renal/thyroid/other cancer, 13/11/9/5/28; median previous irradiated dose, 30 Gy (range, 8-70.4 Gy); median interval from latest irradiation, 21 months (range, 4-192 months); prescribed dose for SBRT, 24 Gy in 2 fractions/30 Gy in 5 fractions/35 Gy in 5 fractions, 51/13/2. Median follow-up after SBRT was 10 months (range, 1-37 months). Fifty-seven patients achieved pain response (86%). The 1-year pain failure-free rate was 55%. Median pain failure-free duration was 13 months (range, 1-24 months). Grade 4 adverse events were observed in six patients (vertebral compression fracture, n = 5; radiation myelopathy, n = 1). No other toxicities of Grade 3 or greater were encountered. CONCLUSIONS: Re-irradiation SBRT has potential to achieve good response and long-term pain control for painful bone metastases. Prospective analysis is necessary to confirm the safety and efficacy of SBRT as re-irradiation.

A comparison of clinical outcomes between three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for prostate cancer.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) reduces the dose delivered to organs at risk. However, there have been few direct comparisons of IMRT with conventional three-dimensional conformal radiotherapy (3DCRT). The aim of this study was to evaluate the clinical benefit of IMRT in terms of toxicity and biochemical control. METHODS: The medical records of 203 consecutive patients with localized to non-metastatic (stage T1a-T3bN0M0) prostate cancer between 2007 and 2011 were retrospectively reviewed. The prescribed dose was 76 Gy delivered in 38 fractions in both the 3DCRT and IMRT treatment groups. The frequency of grade 2 or greater late gastrointestinal (GI) and genitourinary toxicity and biochemical control were estimated by the log-rank test and Cox proportional hazards model with and without adjustment by the propensity score for treatment choice. RESULTS: A total of 159 patients were included in the study (3DCRT: 70 patients, IMRT: 89 patients). The median follow-up period was 4.7 years. The estimated 5-year cumulative risk of late GI toxicity was significantly lower in the IMRT group than in the 3DCRT group (3.6 vs 13.2%, respectively, p = 0.022). After adjustment by propensity score, IMRT remained associated with a lower risk of late GI toxicity (hazard ratio 0.22; 95% confidence interval 0.058-0.85; p = 0.028). The 5-year biochemical failure-free rate was 93.2% in the 3DCRT group and 95.4% in the IMRT group (non-significant difference). CONCLUSIONS: The incidence of late GI toxicity was significantly lower in the IMRT group than in the 3DCRT group, while the biochemical control rates were no different between the two groups. These clinical data suggest the benefit of IMRT in the reduction of late GI toxicity.

Autologous Peripheral Blood Stem Cell Transplantation and Timing of Local Radiation Therapy in Patients With Malignant Lymphoma: Results of the Japanese Radiation Oncology Study Group Questionnaire Survey.

BACKGROUND/AIM: Malignant lymphoma (ML) including Hodgkin's lymphoma and non-Hodgkin's lymphoma is often treated with local radiation therapy (RT) in combination with autologous hematopoietic stem cell transplantation (ASCT) to prevent relapse; however, the efficacy and optimal timing of this approach is unclear. In this study, a national survey conducted by the Japanese Radiation Oncology Study Group reviewed ML cases from 2011 to 2019 to determine whether RT should be added to ASCT, focusing on the use of autologous peripheral blood stem cell transplantation (auto-PBSCT), a predominant form of ASCT. PATIENTS AND METHODS: The survey encompassed 92 patients from 11 institutes, and assessed histological ML types, treatment regimens, timing of RT relative to auto-PBSCT, and associated adverse events. RESULTS: The results indicated no significant differences in adverse events, including myelosuppression, based on the timing of RT in relation to auto-PBSCT. However, anemia was more prevalent when RT was administered before auto-PBSCT, and there was a higher incidence of neutropenia recovery delay in patients receiving RT after auto-PBSCT. CONCLUSION: This study provides valuable insights into the variable practices of auto-PBSCT and local RT in ML treatment, emphasizing the need for optimized timing of these therapies to improve patient outcomes and reduce complications.

Early failure is still a poor prognostic factor in patients with relapsed or refractory large B-cell lymphoma in the era of CAR T-cell therapy.

Patients with refractory or relapsed (R/R) large B-cell lymphoma (LBCL) refractory to first-line chemotherapy or with early relapse have poor outcomes. While chimeric antigen receptor (CAR) T-cell therapy has impressive efficacy after two or more lines of chemotherapy, it's still uncertain if these outcomes remain consistent in the context of third-line CAR T-cell therapy. We conducted a retrospective study of 107 R/R LBCL patients. Patients with relapse 12 months or more after their first-line chemoimmunotherapy (late failure: n = 25) had significantly longer overall survival (OS) than patients with refractory disease or relapse within 12 months (early failure: n = 82) (median OS: not achieved vs. 18.4 months; P < 0.001). Among patients who proceeded to autologous hematopoietic stem-cell transplantation (auto-HSCT), those with late failure had significantly longer event-free survival (EFS) than those with early failure (median EFS: 26.9 vs. 3.1 months; P = 0.012). However, no significant difference in EFS was detected among patients who underwent CAR T-cell therapy (median EFS: not reached vs. 11.8; P = 0.091). Cox regression with restricted cubic spline demonstrated that timing of relapse had significant impact on EFS in patients with auto-HSCT but not in patients with CAR T-cell therapy. Of patients who were scheduled for CAR T-cell therapy, those with late failure were significantly more likely to receive CAR T-cell therapy than those with early failure (90% vs. 57%; P = 0.008). In conclusion, patients with early failure still experienced poor outcomes after the approval of third-line CAR T-cell therapy.

Combination Therapy for a Severe Axillary Keloid with Abscesses: A Case Report.

Keloids are laterally growing fibroproliferative skin disorders. Severe keloids spread widely, sometimes over joints, thus significantly limiting motor function. They are associated with recurrent, very painful draining infections. Here, we report a case of a giant keloid that was successfully treated by combination therapy comprising surgery (partial resection followed by local flap transposition) and subsequent radiotherapy and steroid-plaster therapy. The keloid was first noticed when the patient was 7 years old at the site of a Bacille Calmette-Guérin vaccination she had received on her left shoulder in infancy. The keloid grew rapidly and widely after adulthood. A malignant tumor was suspected at another hospital, but a biopsy at age 45 years indicated the lesion was a keloid. Later, the keloid grew from the shoulder onto the chest and back and over the anterior axilla. At age 62 years, the patient was referred to our hospital. Under general anesthesia, the keloid was partially resected and the wound was covered with a local flap. Postoperative radiotherapy was performed 1 week later. The residual keloid was treated for 18 months with steroid tape. At 18 months after surgery, no recurrence of the keloid was observed. The patient had no pain or movement restriction. She was extremely satisfied with the results and considered the treatment to have improved her quality of life. While a standard strategy for severe keloid remains to be established, combination therapy comprising surgery, postoperative radiotherapy, and steroid-plaster therapy that aims to reduce inflammation and skin tension may be an option.

Preliminary Study on Establishing a Heart Rate Variability-based Method for Objectively Evaluating Bone Metastasis Pain.

BACKGROUND/AIM: The aim of this study was to establish an objective evaluation method for pain due to bone metastasis, based on heart rate variability (HRV). PATIENTS AND METHODS: In this prospective study, patients who underwent radiotherapy for painful bone metastases were enrolled. Pain was assessed using a numerical rating scale (NRS), and anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS). Autonomic and physical activities were evaluated by measuring HRV using a wearable device. NRS, HADS, and R-R interval (RRI) values were obtained upon starting, completing, and 3-5 weeks after radiotherapy. RESULTS: Between July 2020 and July 2021, 11 patients were enrolled. The median average NRS score was 5 (range=2-10). HADS-assessed median anxiety and depression scores were 8 (range=1-13 and 2-21). For patients with an NRS score ≥4, NRS score was significantly associated with low-frequency/high-frequency (LF/HF) component ratio (p=0.03). Heart rate during physical activity was significantly higher than resting heart rate; however, mean resting LF/HF was significantly higher than LF/HF during physical activity. During rest, excluding patients with a HADS depression score ≥7 in an NRS score 1-3, there was a trend for a positive correlation between the NRS score and the mean LF/HF (p=0.07). CONCLUSION: HRV measurements can objectively evaluate pain due to bone metastasis. However, we must consider that the effects of mental status, such as depression, on LF/HF also affect HRV in patients with cancer with mild pain.

Clinical outcomes in transplant-eligible patients with relapsed or refractory diffuse large B-cell lymphoma after second-line salvage chemotherapy: A retrospective study.

OBJECTIVE: The prognosis of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. Although patients who fail first-line salvage chemotherapy are candidates for second-line salvage chemotherapy, the optimal treatment strategy for these patients has not yet been established. METHODS: The present, single-center, retrospective study included transplant-eligible patients with R/R DLBCL who received second-line salvage chemotherapy with curative intent. RESULTS: Seventy-six patients with R/R DLBCL received second-line salvage chemotherapy. Eighteen (23.7%) patients were responders to the first-line salvage chemotherapy. The overall response rate was 39.5%, and overall survival (OS) was significantly longer in patients who responded to second-line salvage chemotherapy than those who did not. Forty-one patients who proceeded to potentially curative treatment (autologous hematopoietic stem cell transplantation [ASCT], chimeric antigen receptor [CAR] T-cell therapy, or allogeneic hematopoietic stem cell transplantation) had a better prognosis than those who did not. Among the 46 patients who failed to respond to the second-line salvage regimen, only 18 (39.1%) could proceed to the curative treatments. However, among the 30 patients who responded to the second-line salvage regimen, 23 (76.7%) received one of the potentially curative treatments. Among 34 patients who received CAR T-cell therapy, OS was significantly longer in those who responded to salvage chemotherapy immediately prior to CAR T-cell therapy than in those who did not respond. In contrast, the number of prior lines of chemotherapy was not identified as a statistically significant prognostic factor of survival. No significant difference was detected in OS between patients receiving ASCT and those receiving CAR T-cell therapy after the response to second-line salvage chemotherapy. DISCUSSION: In this study, we demonstrated that chemosensitivity remained a crucial factor in predicting survival outcomes following CAR T-cell therapy irrespective of the administration timing, and that both ASCT and CAR T-cell therapy were acceptable after the response to second-line salvage chemotherapy.

Chimeric antigen receptor T-cell therapy following autologous transplantation for secondary central nervous system lymphoma: A case report.

RATIONALE: Chimeric antigen receptor (CAR) T-cell therapy is effective in treating relapsed and refractory B-cell non-Hodgkin lymphoma. However, because of the mortality risk associated with immune effector cell-associated neurotoxicity syndrome and pseudoprogression, patients with central nervous system (CNS) involvement are less likely to receive CAR T-cell therapy. PATIENTS CONCERNS: We report a case of a 61-year-old, male patient with intravascular large B-cell lymphoma who suffered a CNS relapse after standard chemotherapy. DIAGNOSIS: A diagnosis of intravascular large B-cell lymphoma with CNS involvement was made. INTERVENTIONS: We treated the patient using CAR T-cell therapy following a conditioning regimen consisting of thiotepa and busulfan and autologous stem cell transplantation. Although he experienced grade 1 cytokine release syndrome, no other serious adverse events, such as immune effector cell-associated neurotoxicity syndrome or pseudoprogression, were observed. OUTCOMES: The patient achieved complete remission after the CAR T-cell infusion. LESSONS: CAR T-cell therapy following autologous stem cell transplantation is a viable option for relapsed/refractory lymphoma with CNS infiltration. Further clinical studies are warranted to verify its safety and efficacy.

Accelerated Hypofractionated Radiotherapy Versus Stereotactic Body Radiotherapy for the Treatment of Stage I Nonsmall Cell Lung Cancer-A Single Institution Experience With Long-Term Follow-Up.

PURPOSE: Although stereotactic body radiation therapy is one of the standard treatments for stage I nonsmall cell lung cancer, in the case of central tumors it carries the risk of severe adverse events for serial organs. Accelerated hypofractionated radiotherapy is considered a reasonable alternative to treat central tumors. We have been treating central tumors with accelerated hypofractionated radiotherapy using a 75 Gy/25 fr/5 weeks regimen, and we compared the results with those of stereotactic body radiation therapy using 48 Gy/4 fr/1 week. METHODS: Patients with central tumors and/or unfit for 1-hour fixation were candidates for accelerated hypofractionated radiotherapy. Based on the proximity to the biologically effective dose at 10 Gy, above accelerated hypofractionated radiotherapy regimen was adopted. RESULTS: From October 2003 to December 2010, 159 patients, who received either accelerated hypofractionated radiotherapy (103 cases) or stereotactic body radiation therapy (56 cases), were included in the analysis. In the accelerated hypofractionated radiotherapy group, 40 (39%) cases were central tumors, whereas all cases were peripheral tumors in the stereotactic body radiation therapy group. Overall 5-year local control and survival rates were 81.9% (95% confidence interval 73.6%-90.1%) and 46.5% (95% confidence interval 36.7%-56.2%), respectively for the accelerated hypofractionated radiotherapy group, and 75.4% (95% confidence interval 63.0%-87.8%) and 44.6% (95% confidence interval 31.6%-57.7%), respectively for the stereotactic body radiation therapy group (n.s.). Among central tumors, ultracentral tumors (21 cases) and the remaining central tumors (19 cases) were similar in both local control and survival. On multivariate analysis, hazard ratios for accelerated hypofractionated radiotherapy versus stereotactic body radiation therapy were <1 for both local control and survival. Pulmonary toxicity was similar in both groups. No serial organ toxicity was observed for central tumors. CONCLUSIONS: Accelerated hypofractionated radiotherapy with a 75 Gy/25 fr/5 weeks regimen is promising in that it can obtain similar local control and survival results to stereotactic body radiation therapy, and it can control both central and peripheral tumors without any serial organ toxicities. Based on these results, prospective multicenter trials are worth conducting, especially for ultracentral tumors.