The role of radiotherapy in patients with refractory Hodgkin's lymphoma after treatment with brentuximab vedotin and/or immune checkpoint inhibitors.

Background: Approximately 10%-30% of patients with Hodgkin's lymphoma (HL) experience relapse or refractory (R/R) disease after first-line standard therapy. Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) have important roles in the salvage treatment of R/R HL. However, subsequent treatment for HL refractory to BV and/or ICI treatment is challenging. Methods: We retrospectively analyzed patients in two institutions who had R/R HL, experienced BV or ICI treatment failure, and received radiotherapy (RT) thereafter. The overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were analyzed. Results: Overall, 19 patients were enrolled. First-line systemic therapy comprised doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD, 84.2%); AVD plus ICIs (10.5%); and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP, 5.3%). After first-line therapy, 15 (78.9%) and four patients (21.1%) had refractory disease and relapsed, respectively. After R/R HL diagnosis, six (31.6%), two (10.5%), and 11 (57.9%) patients received BV and ICIs concurrently, BV monotherapy, and ICI monotherapy, respectively. All patients received intensity-modulated RT (n = 12, 63.2%) or volumetric modulated arc therapy (VMAT; n = 7, 36.8%). The ORR as well as the complete response (CR) rate was 100%; the median DOR to RT was 17.2 months (range, 7.9-46.7 months). Two patients showed progression outside the radiation field; one patient had extensive in-field, out-of-field, nodal, and extranodal relapse. With a median follow-up time of 16.2 months (range, 9.2-23.2 months), the 1-year PFS and OS were 84.4% and 100%, respectively. PFS was associated with extranodal involvement (P = 0.019) and gross tumor volume (P = 0.044). All patients tolerated RT well without adverse events of grade ≥ 3. Conclusion: RT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.

Hypofractionated radiotherapy for refractory or relapsed aggressive B-cell lymphoma in the rituximab era.

BACKGROUND: Radiotherapy (RT) is an effective and available local treatment for patients with refractory or relapsed (R/R) aggressive B-cell lymphomas. However, the value of hypofractionated RT in this setting has not been confirmed. METHODS: We retrospectively analyzed patients with R/R aggressive B-cell lymphoma who received hypofractionated RT between January 2020 and August 2022 at a single institution. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute side effects were analyzed. RESULTS: A total of 30 patients were included. The median dose for residual disease was 36 Gy, at a dose per fraction of 2.3-5 Gy. After RT, the ORR and complete response (CR) rates were 90% and 80%, respectively. With a median follow-up of 10 months (range, 2-27 months), 10 patients (33.3%) experienced disease progression and three died. The 1-year OS and PFS rates for all patients were 81.8% and 66.3%, respectively. The majority (8/10) of post-RT progressions involved out-of-field relapses. Patients with relapsed diseases, no response to systemic therapy, multiple lesions at the time of RT, and no response to RT were associated with out-of-field relapses. PFS was associated with response to RT (P = 0.001) and numbers of residual sites (P < 0.001). No serious non-hematological adverse effects (≥ grade 3) associated with RT were reported. CONCLUSION: These data suggest that hypofractionated RT was effective and tolerable for patients with R/R aggressive B-cell lymphoma, especially for those that exhibited localized residual disease.

The value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma staged with PET/CT.

BACKGROUND: Limited evidence supports the omission of routine bone marrow (BM) examination (biopsy and aspiration) in patients with nasal-type extranodal NK/T-cell lymphoma (ENKTCL). This study was aimed at assessing whether BM examination provides valuable information for positron emission tomography/computed tomography (PET/CT)-based staging in this patient population. PATIENTS AND METHODS: Patients newly diagnosed with ENKTCL who underwent initial staging with both PET/CT and BM examination between 2013 and 2020 were retrospectively identified in two Chinese institutions. Overall, 742 patients were included; the BM examination was positive in 67 patients. RESULTS: Compared with BM biopsy alone, the combination of BM biopsy and aspiration assessment did not afford any additional diagnostic value. No patient with a positive BM biopsy was found to have early-stage disease by PET/CT. BM biopsy or PET/CT led to upstaging from stage III to IV as a result of BM involvement in 21 patients. In 135 patients with distant organ involvement, BM involvement was associated with worse overall survival (OS) and progression-free survival (PFS) compared with the corresponding durations in patients without BM involvement (2-year OS: 35.9% vs. 60.4%, p < .001; PFS: 26% vs. 40.7%, p = .003). No difference in survival was noted between groups judged positive based on PET/CT and BM biopsy. CONCLUSION: Compared with aspiration, BM biopsy led to the detection of more BM lesions. Baseline PET/CT can be safely used to exclude BM involvement in early-stage disease. Overall, routine BM examination affords diagnostic or prognostic value over PET/CT in patients with advanced-stage nasal-type ENKTCL.

Is the irradiated small bowel volume still a predictor for acute lower gastrointestinal toxicity during preoperative concurrent chemo-radiotherapy for rectal cancer when using intensity-modulated radiation therapy?

BACKGROUND: The small bowel (SB) represents the most important dose-limiting structure in pelvic radiotherapy (RT). However, we observed that the majority of rectal cancer patients who received preoperative pelvic intensity modulated RT (IMRT) developed acute tenesmus without watery diarrhea. The objective of this study is to determine if the RT dose to SB affects the acute lower gastrointestinal toxicity (ALGIT) in rectal cancer patients who received neoadjuvant concurrent chemotherapy-IMRT. We will also evaluate if patient and tumor factors affect the ALGIT. METHODS: We retrospectively analyzed 63 rectal cancer patients that consecutively received preoperative IMRT (45 Gy for pelvis and 50 Gy for gross tumor in 25 fractions) with concurrent chemotherapy (oxaliplatin 130 mg/m(2) on day 1 and capecitabine 825 mg/m(2), twice per day from day 1 to day 14, week 1 and 4) between May 2012 and May 2013. The ALGIT was assessed with Common Terminology Criteria for Adverse Events version 3. The patients were stratified into two groups (with and without grade ≥2 ALGIT). The effect of SB volume receiving 5 to 40 Gy (V5 to V40) at a 5 Gy interval dose level on grade ≥2 ALGIT was evaluated. The volume of small bowel is defined as the volume of the small bowel loop. Other factors evaluated include patient's age and gender, tumor size and location and preexisting number of daily bowel movements. RESULTS: Overall, grade ≥2 ALGIT occurred in 57 % (36/63) patients. There was no significant difference between the two groups of patients (with and without grade ≥2 ALGIT) in SB V5 to V40, patient's age and gender, tumor location and preexisting number of daily bowel movements. There was a significant difference between the two groups of patients in tumor volume (with grade ≥2 ALGIT: 115.5 ± 85.5 cm(3) versus without grade ≥2 ALGIT: 58.5 ± 25.2 cm(3), p = 0.0001). Multivariate analysis revealed no association between the dose SB received (V5 to V40) and the grade ≥2 ALGIT after adjusting for the tumor volume. CONCLUSIONS: With IMRT technique used in rectal cancer patients undergoing preoperative chemo-radiotherapy, the acute lower GI toxicity is not associated with small bowel V5 to V40; instead it is associated with rectal tumor size.

Pilot study of intense neoadjuvant chemoradiotherapy for locally advanced rectal cancer: retrospective review of a phase II study.

AIMS AND BACKGROUND: Locally advanced rectal adenocarcinoma is typically treated with neoadjuvant chemoradiotherapy and surgery. We assessed the effect of an additional cycle of capecitabine/oxaliplatin chemotherapy before surgery in 57 patients with T3/4, N+/- or T1/2, N+ rectal cancer. MATERIALS AND STUDY DESIGN: Radiotherapy (total dose, 50.4 Gy) was combined with three cycles of chemotherapy (two cycles concomitant with radiotherapy), and each cycle consisted of oxaliplatin (130 mg/m2 on day 1) and capecitabine (825 mg/m2, twice per day from day 1 to day 14) for 21 days. In addition to assessing the safety of this treatment, the primary endpoint was pathological complete response (pCR). The secondary endpoint was the change in primary tumor and node stage from pre-treatment to post-surgery. RESULTS: Eleven patients (19%) experienced complete tumor regression and 23 patients (40%) experienced tumor regression grade 3. Tumor down-staging occurred in 31 patients (54.4%) and down-staging of nodes occurred in 25 patients (43.9%). There was a significant difference in tumor stage between pre-treatment and post-surgery (P <0.001). Patients with less advanced N stages had significantly better recurrence-free survival but similar metastasis-free survival and overall survival. Tumor regression grade was not associated with overall survival, recurrence-free survival or metastasis-free survival. The most common adverse events were pulmonary infection (n = 6, 10.5%) and intestinal obstruction (n = 6, 10.5%): CONCLUSIONS. An additional cycle of chemotherapy given after chemoradiotherapy and before surgery provided good efficacy and had a satisfactory safety profile in patients with locally advanced rectal cancer.

Value of magnetic resonance diffusion-weighted imaging for the prediction of radiosensitivity in nasopharyngeal carcinoma.

OBJECTIVE: The effectiveness of radiotherapy in nasopharyngeal carcinoma (NPC) is closely related to the radiosensitivity of the carcinoma; however, there is currently no effective method to predict radiosensitivity in NPC. We explored the predictive value of magnetic resonance diffusion-weighted imaging (MR-DWI) for radiosensitivity in NPC. Study Design Prospective cohort study. Setting Single hospital. SUBJECTS AND METHODS: Patients with NPC who received intensity-modulated radiotherapy (IMRT) with or without chemotherapy were enrolled from April 2010 through November 2011. Primary tumor apparent diffusion coefficient (ADC) was measured before treatment (ADC0) and 2 weeks after the start of IMRT (ADC1). ADC change (ΔADC) was calculated as (ADC1 - ADC0)/ADC0 * 100%. Three months after the end of radiotherapy, the short-term effect of radiotherapy was assessed using the World Health Organization's response evaluation criteria in solid tumors. RESULTS: Of 134 eligible NPC patients, 121 received combination chemotherapy. Three months after radiotherapy, residual local tumors were detected in 23 (17.2%) cases, and no residual tumors were detected in 111 (82.8%) cases. There was no significant difference in the residual tumor rates of patients receiving combination chemotherapy vs those who did not (P = 1.000). There were no significant differences in the ADC0 or ADC1 values of patients with and without residual tumors (P = .083 and .262). The ΔADC values of patients with (49.77% ± 31.02%) and without (68.35% ± 34.22%) residual tumors were significantly different (t = -2.406, P = .017). Logistic regression analysis indicated that ΔADC was an independent prognostic factor for the short-term effect of IMRT in NPC. CONCLUSION: Magnetic resonance diffusion-weighted imaging may potentially have value for predicting radiosensitivity in NPC.

Prognostic significance of expression of cyclooxygenase-2, vascular endothelial growth factor, and epidermal growth factor receptor in nasopharyngeal carcinoma.

BACKGROUND: The association between expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and the long-term outcomes in treated nasopharyngeal carcinoma (NPC) was studied. METHODS: Expression of COX-2, VEGF, and EGFR by immunohistochemical (IHC) staining was assessed in 128 patients with NPC. Overall survival (OS), disease-free survival (DFS), locoregional control, and distant metastasis-free survival rates were compared for different expression levels of each marker. Multivariate analysis was by the Cox regression model. RESULTS: Median follow-up after radiation therapy ± chemotherapy was 116 months. Univariate and multivariate analyses demonstrated that COX-2, VEGF, EGFR, and clinical stage were all independent predictors for OS, DFS, locoregional control, and distant metastasis-free survival rates. CONCLUSIONS: High expression of COX-2, VEGF, and EGFR were independent adverse prognostic factors for long-term outcomes in nonmetastatic NPC independent of clinical stage.