Multicenter phase II study of moderate low-dose radiotherapy in indolent non-Hodgkin lymphoma: CLCG-iNHL-01 protocol.

Background: Radiotherapy is an effective treatment for indolent non-Hodgkin lymphoma (iNHL); however, the optimal radiotherapy dose remains to be determined. We hypothesize that a suitable dose may exist between 4 and 24 Gy. Methods: This prospective multicenter phase II trial intends to recruit 73 sites of iNHL patients, who will receive involved-site radiotherapy of 12 Gy in four fractions. The primary objective is the 6-month clinical complete response rate. Tumor tissue, blood and conjunctival specimens will be collected to identify potential predictive biomarkers. Discussion: The CLCG-iNHL-01 trial will evaluate the efficacy and toxicity of 12 Gy in patients with iNHL and provide information on a novel hypofractionation regimen of low-dose radiotherapy. Clinical Trial Registration: NCT05543070 (ClinicalTrials.gov).

Preoperative chemoradiotherapy in older patients with rectal cancer guided by comprehensive geriatric assessment within a multidisciplinary team-a multicenter phase II trial.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as "fit" by comprehensive geriatric assessment (CGA). METHODS: A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of "fit" (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22). RESULTS: One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47). CONCLUSION: This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA. TRIAL REGISTRATION: The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).

The prognostic value of tumour-infiltrating lymphocytes, programmed cell death protein-1 and programmed cell death ligand-1 in Stage I-III triple-negative breast cancer.

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) represent a robust biological prognostic biomarker in triple-negative breast cancer (TNBC); however, the contribution of different subsets of immune cells is unclear. We investigated the prognostic value of immune markers, including stromal TILs (sTILs), CD8+T and FOPX3+T cells, PD-1 and PD-L1 in non-metastatic TNBC. METHODS: In total, 259 patients with Stage I-III TNBC were reviewed. The density of sTILs along with the presence of total (t), stromal (s), and intratumoral (i) CD8+T cells and FOPX3+T cells were evaluated by haematoxylin and eosin and immunohistochemical staining. Immunohistochemical staining of PD-1, PD-L1 was also conducted. RESULTS: All immune markers were positively correlated with each other (P < 0.05). In the multivariate analysis, sTILs (P = 0.046), tCD8+T cells (P = 0.024), iCD8+T cells (P = 0.050) and PD-1 (P = 0.039) were identified as independent prognostic factors for disease-free survival (DFS). Further analysis showed that tCD8+T cells (P = 0.026), iCD8+T cells (P = 0.017) and PD-1 (P = 0.037) increased the prognostic value for DFS beyond that of the classic clinicopathological factors and sTILs. CONCLUSIONS: In addition to sTILs, inclusion of tCD8+T, iCD8+T cells, or PD-1 may further refine the prognostic model for non-metastatic TNBC beyond that including classical factors alone.

Risk stratification and prognostic value of multi-modal MRI-based radiomics for extranodal nasal-type NK/T-cell lymphoma.

BACKGROUND: Magnetic resonance imaging (MRI) performs well in the locoregional assessment of extranodal nasal-type NK/T-cell lymphoma (ENKTCL). It's important to assess the value of multi-modal MRI-based radiomics for estimating overall survival (OS) in patients with ENKTCL. METHODS: Patients with ENKTCL in a prospectively cohort were systemically reviewed and all the pretreatment MRI were acquisitioned. An unsupervised spectral clustering method was used to identify risk groups of patients and radiomic features. A nomogram-revised risk index (NRI) plus MRI radiomics signature (NRI-M) was developed, and compared with the NRI. RESULTS: The 2 distinct type I and II groups of the MRI radiomics signatures were identified. The 5-year OS rates between the type I and type II groups were 87.2% versus 67.3% (P = 0.002) in all patients, and 88.8% versus 69.2% (P = 0.003) in early-stage patients. The discrimination and calibration of the NRI-M for OS prediction demonstrated a better performance than that of either MRI radiomics or NRI, with a mean area under curve (AUC) of 0.748 and 0.717 for predicting the 5-year OS in all-stages and early-stage patients. CONCLUSIONS: The NRI-M model has good performance for predicting the prognosis of ENKTCL and may help design clinical trials and improve clinical decision making.

Phase 2 Study of Adjuvant Radiotherapy Following Narrow-Margin Hepatectomy in Patients With HCC.

BACKGROUND AND AIMS: Surgical resection is the primary treatment for HCC; however, it is associated with a high rate of recurrence and death. We conducted this phase 2 study to investigate the efficacy and safety of postoperative intensity-modulated radiotherapy (IMRT) for HCC after narrow-margin hepatectomy. APPROACH AND RESULTS: We designed a single-arm, prospective phase 2 trial to evaluate overall survival (OS), disease-free survival (DFS), recurrence patterns, and toxicity in patients receiving adjuvant radiotherapy. The eligibility criteria included the following: pathological diagnosis of HCC after hepatectomy, with narrow pathological margins (< 1 cm); age > 18 years; and Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients received IMRT within 4-6 weeks after surgical resection. This trial was registered at ClinicalTrials.gov (NCT01456156). Between 2008 and 2016, a total of 76 eligible patients who underwent narrow-margin resection were enrolled. The median follow-up duration was 70 months; the 3-year OS and DFS rates were 88.2% and 68.1%, respectively; and the 5-year OS and DFS rates were 72.2% and 51.6%, respectively. Intrahepatic recurrence was the primary recurrence pattern. No marginal recurrence was found. Intrahepatic, extrahepatic, and combined recurrences at the first relapse were found in 33, 5, and 1 patient, respectively. The most common radiation-related grade-3 toxicities were leukopenia (7.9%), elevated alanine aminotransferase (3.9%) and aspartate aminotransferase (2.6%) levels, and thrombocytopenia (1.3%). Classical or nonclassical radiation-induced liver disease was not noted. CONCLUSIONS: Adjuvant radiotherapy is an effective, well-tolerated, and promising adjuvant regimen in patients with HCC who have undergone narrow-margin hepatectomy. Our trial provides evidence and a rationale for planning a future phase 3 trial.

POstmastectomy radioThErapy in Node-posiTive breast cancer with or without Internal mAmmary nodaL irradiation (POTENTIAL): a study protocol for a multicenter prospective phase III randomized controlled trial.

BACKGROUND: Various randomized trials have demonstrated that postmastectomy radiotherapy (RT) to the chest wall and comprehensive regional nodal areas improves survival in patients with axillary node-positive breast cancer. Controversy exists as to whether the internal mammary node (IMN) region is an essential component of regional nodal irradiation. Available data on the survival benefit of IMN irradiation (IMNI) are conflicting. The patient populations enrolled in previous studies were heterogeneous and most studies were conducted before modern systemic treatment and three-dimensional (3D) radiotherapy (RT) techniques were introduced. This study aims to assess the efficacy and safety of IMNI in the context of modern systemic treatment and computed tomography (CT)-based RT planning techniques. METHODS: POTENTIAL is a prospective, multicenter, open-label, parallel, phase III, randomized controlled trial investigating whether IMNI improves disease-free survival (DFS) in high-risk breast cancer with positive axillary nodes (pN+) after mastectomy. A total of 1800 patients will be randomly assigned in a 1:1 ratio to receive IMNI or not. All patients are required to receive ≥ six cycles of anthracycline and/or taxane-based chemotherapy. Randomization will be stratified by institution, tumor location (medial/central vs. other quadrants), the number of positive axillary nodes (1-3 vs. 4-9 vs. ≥10), and neoadjuvant chemotherapy (yes vs. no). Treatment will be delivered with CT-based 3D RT techniques, including 3D conformal RT, intensity-modulated RT, or volumetric modulated arc therapy. The prescribed dose is 50 Gy in 25 fractions or 43.5 Gy in 15 fractions. Tiered RT quality assurance is required. After RT, patients will be followed up at regular intervals. Oncological and toxilogical outcomes, especially cardiac toxicities, will be assessed. DISCUSSION: This trial design is intended to overcome the limitations of previous prospective studies by recruiting patients with pN+ breast cancer, using DFS as the primary endpoint, and prospectively assessing cardiac toxicities and requiring RT quality assurance. The results of this study will provide high-level evidence for elective IMNI in patients with breast cancer after mastectomy. TRIAL REGISTRATION: ClinicalTrails.gov , NCT04320979 . Registered 25 Match 2020, https://clinicaltrials.gov/ct2/show/NCT04320979.

Nomogram predicting survival as a selection criterion for postmastectomy radiotherapy in patients with T1 to T2 breast cancer with 1 to 3 positive lymph nodes.

BACKGROUND: The role of postmastectomy radiotherapy (PMRT) in women with pT1-T2N1 breast cancer is controversial. The authors developed a nomogram that was predictive for overall survival (OS) and identified patients who derived no benefit from PMRT. METHODS: The authors retrospectively evaluated 4869 patients with pT1-T2N1 breast cancer who were treated with mastectomy between 2000 and 2014 in 11 Chinese hospitals. Rates of locoregional recurrence and distant metastasis were calculated using competing risk analysis, and disease-free survival and OS rates were calculated using the Kaplan-Meier method. Based on the risk factors identified from Cox regression analysis in 3298 unirradiated patients, a nomogram predicting OS was developed. The benefit of PMRT was evaluated in different risk groups stratified by the nomogram model. RESULTS: After a median follow-up of 65.9 months, the 5-year OS, disease-free survival, locoregional recurrence, and distant metastasis rates were 93.3%, 84.3%, 5.2%, and 8.3%, respectively. A total of 1571 patients (32.3%) underwent PMRT. On multivariable analyses, PMRT was found to increase OS significantly (hazard ratio, 0.61; P = .002). An OS prediction nomogram evaluated the effect of age; tumor location; tumor size; positive lymph node ratio; estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status; and treatment with trastuzumab. Based on nomogram scores, the entire patient cohort was classified into 3 risk groups. PMRT significantly improved the OS of patients in the intermediate-risk (P < .001) and high-risk groups (P = .004), but not in the low-risk group (P = .728). CONCLUSIONS: The authors developed a nomogram that is predictive of OS among women with pT1-T2N1 breast cancer after mastectomy. This nomogram may help to select a subgroup of patients with a good prognosis who will not benefit from PMRT.

Radiotherapy plays an important role in improving the survival outcome in patients with T1-2N1M0 breast cancer - a joint analysis of 4262 real world cases from two institutions.

BACKGROUND: To compare the survival outcomes between breast-conserving surgery (BCS) and modified radical mastectomy (MRM), and to investigate the role of radiotherapy (RT) in patients with pT1-2N1M0 breast cancer. METHODS: A total of 4262 women with T1-2N1M0 breast cancer treated at two institutions were retrospectively reviewed. A total of 3858 patients underwent MRM, and 832 (21.6%) of them received postoperative RT (MRM + RT). A total of 404 patients received BCS plus postoperative RT (BCS + RT). All patients received axillary lymph node dissection, while 3.8% of them had upfront sentinel node biopsy. The association of survival outcomes with different surgical modalities (BCS vs. MRM) and the role of RT were evaluated using multivariable proportional hazards regression and confirmed by the propensity score-matching (PSM) method. RESULTS: At a median follow-up of 71 months (range of 6-230 months), the 5-year overall survival (OS) rates of the BCS and MRM groups were 96.5 and 92.7%, respectively (P = .001), and the corresponding 5-year disease-free-survival (DFS) and locoregional recurrence (LRR) rates were 92.9 and 84.0%, and 2.0 and 7.0% (P = .001), respectively (P < .001). Multivariate analysis revealed that RT was an independent prognostic factor for improved OS (P = .001) and DFS (P = .009), and decreased LRR (P < .001). However, surgery procedure was not independently associated with either OS (P = .495), DFS (P = .204), or LRR (P = .996), which was confirmed by PSM analysis. CONCLUSION: Postoperative radiotherapy rather than the surgery procedures was associated with superior survival outcomes in patients with T1-2N1M0 breast cancer.

Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial.

BACKGROUND: To our knowledge, no randomised study has compared postmastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy in patients with breast cancer. This study aimed to determine whether a 3-week schedule of postmastectomy hypofractionated radiotherapy is as efficacious and safe as a 5-week schedule of conventional fractionated radiotherapy. METHODS: This randomised, non-inferiority, open-label, phase 3 study was done in a single academic hospital in China. Patients aged 18-75 years who had undergone mastectomy and had at least four positive axillary lymph nodes or primary tumour stage T3-4 disease were eligible to participate. Patients were randomly assigned (1:1) according to a computer-generated central randomisation schedule, without stratification, to receive chest wall and nodal irradiation at a dose of 50 Gy in 25 fractions over 5 weeks (conventional fractionated radiotherapy) or 43·5 Gy in 15 fractions over 3 weeks (hypofractionated radiotherapy). The modified intention-to-treat population (including all eligible patients who underwent randomisation but excluding those who were considered ineligible or withdrew consent after randomisation) was used in primary and safety analyses. The primary endpoint was 5-year locoregional recurrence, and a 5% margin was used to establish non-inferiority (equivalent to a hazard ratio <1·883). This trial is registered at ClinicalTrials.gov, number NCT00793962. FINDINGS: Between June 12, 2008, and June 16, 2016, 820 patients were enrolled and randomly assigned to the conventional fractionated radiotherapy group (n=414) or hypofractionated radiotherapy group (n=406). 409 participants in the conventional fractionated radiotherapy group and 401 participants in the hypofractionated radiotherapy group were included in the modified intention-to-treat analyses. At a median follow-up of 58·5 months (IQR 39·2-81·8), 60 (7%) patients had developed locoregional recurrence (31 patients in the hypofractionated radiotherapy group and 29 in the conventional fractionated radiotherapy group); the 5-year cumulative incidence of locoregional recurrence was 8·3% (90% CI 5·8-10·7) in the hypofractionated radiotherapy group and 8·1% (90% CI 5·4-10·6) in the conventional fractionated radiotherapy group (absolute difference 0·2%, 90% CI -3·0 to 2·6; hazard ratio 1·10, 90% CI 0·72 to 1·69; p<0·0001 for non-inferiority). There were no significant differences between the groups in acute and late toxicities, except that fewer patients in the hypofractionated radiotherapy group had grade 3 acute skin toxicity than in the conventional fractionated radiotherapy group (14 [3%] of 401 patients vs 32 [8%] of 409 patients; p<0·0001). INTERPRETATION: Postmastectomy hypofractionated radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with high-risk breast cancer. Hypofractionated radiotherapy could provide more convenient treatment and allow providers to treat more patients. FUNDING: National Key Projects of Research and Development of China; the Chinese Academy of Medical Science Innovation Fund for Medical Sciences; and Beijing Marathon of Hope, Cancer Foundation of China.

Outcomes after hypofractionated stereotactic radiotherapy for colorectal cancer oligometastases.

BACKGROUND AND OBJECTIVES: To assess the efficacy and the effect of biologic effective dose (BED) on outcomes treated by hypofractionated stereotactic radiotherapy for colorectal cancer (CRC) oligometastases. METHODS: Patients with CRC oligometastases treated at our hospital between 2009 and 2016 were included. The relationship between BED and risk of local recurrence was assessed. Recursive partitioning analysis (RPA) was used to evaluate the effect of BED on outcomes. RESULTS: A total of 48 patients were included in this study. Median follow-up time of surviving patient was 15 months (range, 3-82 months). The 1-year local control rate was 85%. The risk of local recurrence decreased sharply when BED was >90 Gy10 . RPA showed BED of 100 Gy 10 was the appropriate dose for recurrence risk stratification. BED ≥ 100 Gy 10 was significantly better than BED < 100 Gy 10 for achieving 1-year local control (94.4% vs 63.2%; P = 0.022) and 1-year OS (100% vs 73.4%; P = 0.028). One patient who received long-term antiangiogenic treatment died of massive intestinal hemorrhage; no other grade 3 or above early or late events were observed. CONCLUSIONS: Hypofractionated stereotactic radiotherapy provides favorable outcomes with acceptable toxicities in CRC oligometastases. BED ≥ 100 Gy is associated with better outcomes.

Patients with pathological stage N2 rectal cancer treated with early adjuvant chemotherapy have a lower treatment failure rate.

BACKGROUND: In this era of oxaliplatin-based adjuvant therapy, the optimal sequence in which chemoradiotherapy should be administered for pathological stage N2 rectal cancer is unknown. The aim of this study was to investigate this sequence. METHODS: In the primary adjuvant concurrent chemoradiotherapy (A-CRT) group (n = 71), postoperative concurrent chemoradiotherapy was administered before adjuvant chemotherapy. In the primary adjuvant chemotherapy (A-CT) group (n = 43), postoperative concurrent chemoradiotherapy was administered during or after adjuvant chemotherapy. Postoperative radiotherapy comprised 45-50.4 Gy in 25-28 fractions. Concurrent chemotherapy comprised two cycles of oral capecitabine (1,600 mg/m2) on days 1-14 and 22-35. Patients receiving adjuvant chemotherapy with four or more cycles of XELOX (oxaliplatin plus capecitabine) or eight or more cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were included. RESULTS: Between June 2005 and December 2013, data for 114 qualified rectal cancer patients were analyzed. The percentages of patients in whom treatment failed in the A-CRT and A-CT groups were 33.8% and 16.3%, respectively (p = 0.042). More patients had distant metastases in the A-CRT group than in the A-CT group (32.4% vs. 14.3%, p = 0.028). Multivariate analysis indicated that the sequence in which chemoradiotherapy was administered (A-CT vs. A-CRT) was an independent prognostic factor for both estimated disease-free survival [hazard ratio (HR) 0.345, 95% confidence interval (CI) 0.137-0.868, p = 0.024] and estimated distant metastasis-free survival (HR 0.366, 95% CI 0.143-0.938, p = 0.036). CONCLUSIONS: In pathological stage N2 rectal cancer patients, administering adjuvant chemotherapy before chemoradiotherapy led to a lower rate of treatment failure, especially with respect to distant metastasis. Adjuvant chemotherapy prescribed as early as possible might benefit this cohort of patients in this era of oxaliplatin-based adjuvant therapy.

Clinical and prognostic differences between ALK-negative anaplastic large cell lymphoma and peripheral T cell lymphoma, not otherwise specified: a single institution experience.

Clinical differences between anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALK(-) ALCL) and peripheral T cell lymphoma, not otherwise specified (PTCL-NOS), remain unclear. The aim of this study was to compare the clinical and prognostic features of these two lymphoma types. We retrospectively analyzed 167 patients with ALK(-) ALCL (n = 48) and PTCL-NOS (n = 119). Compared with ALK(-) ALCL patients, PTCL-NOS patients exhibited distinct differences in clinical features with a propensity for more advanced stages, frequent extranodal involvement, and a poor performance status, leading to a higher risk group according to the International Prognostic Index or Prognostic Index for PTCL-NOS. Patients with ALK(-) ALCL were associated with a higher complete response rate (47.9 vs. 31.0 %; P = 0.041) after initial chemotherapy than patients with PTCL-NOS. The prognosis was significantly different between two subtypes, with a 5-year overall survival (OS) rate of 57.9 % for ALK(-) ALCL and 23.9 % for PTCL-NOS (P = 0.002). The subgroup analysis showed significant differences in OS and progression-free survival between the two subtypes in early-stage diseases, but not in advanced-stage diseases. We conclude that patients with ALK(-) ALCL showed favorable clinical features, higher chemosensitivity, and a superior outcome than those with PTCL-NOS.

Survival benefit with IMRT following narrow-margin hepatectomy in patients with hepatocellular carcinoma close to major vessels.

BACKGROUND & AIMS: To investigate the role of post-operative intensity-modulated radiotherapy (IMRT) in patients receiving narrow-margin hepatectomy for hepatocellular carcinoma (HCC) located close to the major vessels. METHODS: This exploratory study involved 181 HCC patients. Of them, 116 were treated with narrow-margin (<1.0 cm) hepatectomy. Thirty-three of the 116 underwent postoperative IMRT (Group A), while 83 did not receive radiotherapy (Group B). The remaining 65 patients underwent wide-margin (≥1.0 cm) hepatectomy (Group C). Prognosis and patterns of recurrence were assessed in the three groups. RESULTS: The 3-year overall survival (OS) and disease-free survival (DFS) rates were 89.1 and 64.2% in Group A, 67.7 and 52.2% in Group B and 86.0 and 60.1% in Group C respectively. The OS and DFS of Group A and Group C patients surpassed those of Group B patients (Group A vs. B, P = 0.009 and P = 0.038; and Group C vs. B, P = 0.002 and P = 0.010). Patients in Groups A and C experienced significantly fewer early recurrences than did patients in Group B (P = 0.002). Furthermore, patients in Groups A and C experienced substantially fewer intrahepatic marginal (P = 0.048) and diffuse recurrences (P = 0.018) and extrahepatic metastases (P = 0.038) than did patients in Group B. No patient developed radiation-induced liver disease. CONCLUSIONS: Post-operative IMRT following narrow-margin hepatectomy may be a favourable therapy for both its safety profile and clinical benefit in patients with HCC located close to the major vessels.

Clinical implications of plasma Epstein-Barr virus DNA in early-stage extranodal nasal-type NK/T-cell lymphoma patients receiving primary radiotherapy.

The clinical value of plasma Epstein-Barr virus (EBV) DNA has not been evaluated in patients with early-stage extranodal nasal-type NK/T-cell lymphoma (NKTCL) receiving primary radiotherapy. Fifty-eight patients with stage I disease and 11 with stage II disease were recruited. High pretreatment EBV-DNA concentrations were associated with B-symptoms, elevated lactate dehydrogenase levels, and a high International Prognostic Index score. EBV-DNA levels significantly decreased after treatment. The 3-year overall survival (OS) rate was 82.6% for all patients. Stage I or II patients with a pretreatment EBV-DNA level of ≤ 500 copies/mL had 3-year OS and progression-free survival (PFS) rates of 97.1% and 79.0%, respectively, compared with 66.3% (P = .002) and 52.2% (P = .045) in patients with EBV-DNA levels of > 500 copies/mL. The 3-year OS and PFS rates for patients with undetectable EBV-DNA after treatment was significantly higher than patients with detectable EBV-DNA (OS, 92.0% vs 69.8%, P = .031; PFS, 77.5% vs 50.7%, P = .028). Similar results were observed in stage I patients. EBV-DNA levels correlate with tumor load and a poorer prognosis in early-stage NKTCL. The circulating EBV-DNA level could serve both as a valuable biomarker of tumor load for the accurate classification of early-stage NKTCL and as a prognostic factor.

A prospective phase II clinical trial of total neoadjuvant therapy for locally advanced gastric cancer and gastroesophageal junction adenocarcinoma.

To investigate the safety and efficacy of the neoadjuvant chemoradiotherapy (NCRT) followed by neoadjuvant consolidation chemotherapy (NCCT) and surgery for locally advanced gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma. Patients diagnosed as locally advanced GC or Siewert II/III GEJ adenocarcinoma with clinical stage T3-4 and/or N positive were prospectively enrolled. Patients underwent NCRT (45 Gy/25 fractions) with concurrent S-1, followed by NCCT (4 to 6 cycles of the SOX regimen) 2 to 4 weeks after NCRT. Gastric cancer radical resection with D2 lymph node dissection was performed 4 to 6 weeks after the total neoadjuvant therapy. The study was conducted from November 2019 to January 2023, enrolling a total of 46 patients. During the NCRT, all patients completed the treatment without dose reduction or delay. During the NCCT, 32 patients (69.6%) completed at least 4 cycles of chemotherapy. Grade 3 or higher adverse events in NCRT (5 cases) were non-hematological. During the course of NCCT, a notable occurrence of hematological toxicities was observed, with grade 3 or higher leukopenia (9.7%) and thrombocytopenia (12.2%) being experienced. A total of 28 patients (60.9%) underwent surgery, achieving R0 resection in all cases. A significant proportion of cases (71.4%) exhibited pathological downstaging to ypT0-2, while 10 patients (35.7%) demonstrated a pathologic complete response (pCR). The total neoadjuvant therapy comprising NCRT followed by NCCT and surgery demonstrates a low severe adverse reactions and promising efficacy, which could be considered as a viable treatment for locally advanced GC or GEJ adenocarcinoma.Trial registration: Clinicaltrials.gov (registration number: NCT04062058); the full date of first trial registration was 20/08/2019.

Optimizing the prognostic capacity of baseline 18F-FDG PET/CT metabolic parameters in extranodal natural killer/T-cell lymphoma by using relative and absolute thresholds.

Objectives: To investigate the prognostic capacity of baseline 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters in extranodal natural killer/T-cell lymphoma (ENKTCL), and the influence of relative thresholds (RT) and absolute thresholds (AT) selection on prognostic capacity. Materials and methods: Metabolic tumor volume (MTV)-based parameters were defined using RTs (41 % or 25 % of maximum standardized uptake value [SUVmax]), ATs (SUV 2.5, 3.0, 4.0, or mean liver uptake) in 133 patients. Metabolic parameters were classified into avidity-related parameters (SUVmax, mean SUV [SUVmean], standard deviation of SUV [SUVsd]), volume-related parameters (RT-MTV), and avidity- and volume-related parameters (total lesion glycolysis [TLG] and AT-MTV). The prognostic capacity of the metabolic parameters and the effects of different threshold types (RT vs. AT) were evaluated. Results: All metabolic parameters were moderately associated with prognosis. However, the area under the receiver operating characteristic curve of MTV and TLG was slightly higher than that of avidity-related parameters for predicting 5-year progression-free survival (PFS) (0.614-0.705 vs. 0.563-0.609) and overall survival (OS) (0.670-0.748 vs. 0.562-0.593). Correlations of MTV and avidity-related parameters differed between RTs (r < 0.06, P = 0.324-0.985) and ATs (r 0.56-0.84, P ≤ 0.001). AT-MTV was the optimal predictor for PFS and OS, while RT-TLG was the optimal predictor for PFS, and the combination of RT-MTV with SUVmax was the optimal predictor for OS. Conclusion: The incorporation of volume and avidity significantly improved the prognostic capacity of PET in ENKTCL. Composite parameters that encompassed both avidity and volume were recommended.

Prognostic value of lymphocytes in patients with breast cancer receiving radiotherapy after breast-conserving surgery: A post hoc analysis of a phase III randomized trial.

PURPOSE: To evaluate the prognostic value of peripheral lymphocyte count (PLC) in the breast cancer patients after breast-conserving surgery (BCS) with radiotherapy (RT). METHODS AND MATERIALS: This post hoc analysis was performed using data of 628 patients from a phase III, randomized controlled trial comparing hypofractionated RT (HFRT) with conventional fractionated RT (CFRT) after BCS. PLCs were obtained before, during, and after RT until the 1-year follow-up. The optimal cut-off PLCs were determined using the maxstat package in R. Survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. RESULTS: A total of 275 (46.1 %) patients developed lymphopenia during RT, among them, 17 (2.8 %) had grade 3 lymphopenia and no one developed grade 4 lymphopenia. With a median follow-up of 110.8 months, patients with pre-RT PLCs of < 1.77 × 109/L had a significantly lower 10-year breast cancer-specific survival (BCSS) rate (P = 0.013) and overall survival (OS) rate (P = 0.026). Patients with a nadir PLC of < 1.35 × 109/L had a significantly poorer 10-year OS rate (P = 0.048). Multivariate analysis showed that a pre-RT PLC of < 1.77 × 109/L was an independent factor influencing BCSS and OS, while the effect of the nadir PLC did not remain significant. Neither PLC nor lymphopenia recovery at post-RT 1, 3, and 6 months and 1 year was associated with survival. CONCLUSIONS: Radiation-induced lymphopenia in patients with breast cancer after BCS tends to be mild. The lower pre-RT PLC predicted poorer survival.

Dosimetric benefit and clinical feasibility of deep inspiration breath-hold and volumetric modulated arc therapy-based postmastectomy radiotherapy for left-sided breast cancer.

To evaluate the dosimetric benefits and clinical feasibility of deep inspiratory breath-hold (DIBH) combined with volumetric modulated arc therapy (VMAT) in left-sided postmastectomy radiotherapy (PMRT). Eligible patients with left-sided breast cancer undergoing DIBH-based PMRT were prospectively included. Chest wall, supra/infraclavicular fossa, and/or internal mammary node irradiation (IMNI) were planned with a prescription dose of 43.5 Gy in 15 fractions. VMAT plans were designed on free breathing (FB)-and DIBH-CT to compare dosimetric parameters in heart, left anterior descending artery (LAD) and lung. Cone-beam computed tomography (CBCT) was performed before and after treatment to evaluate inter- and intra-fractional setup errors. Heart position and dose variations during treatment were estimated by fusing CBCT with DIBH-CT scans.Twenty patients were included with 10 receiving IMNI. In total, 193 pre-treatment and 39 pairs pre- and post-treatment CBCT scans were analyzed. The Dmean, Dmax, and V5-40 of the heart, LAD, and left lung were significantly lower in DIBH than FB (p < 0.05 for all), except for V5 of LAD (p = 0.167). The cardiopulmonary dosimetric benefits were maintained regardless of IMNI. The inter- and intra-fractional setup errors were < 0.3 cm; and the overall estimated PTV margins were < 1.0 cm. During treatment, the mean dice similarity coefficient of heart position and the mean ratio of heart Dmean between CBCT and DIBH-CT plans was 0.95 (0.88-1.00) and 100% (70.6-119.5%), respectively. DIBH-VMAT could effectively reduce the cardiopulmonary doses with acceptable reproducibility and stability in left-sided PMRT regardless of IMNI.

Treatment outcome, toxicity, and quality of life of patients with bronchus-associated lymphoid tissue lymphoma.

The disease failure patterns and optimal treatment of bronchus-associated lymphoid tissue (BALT) lymphoma are unknown. This retrospective study involved 71 patients with primary BALT lymphoma who had received radiotherapy (RT), surgery, immunochemotherapy (IC), or observation. The median follow-up time was 66 months. The 5-year overall survival and lymphoma-specific survival were 91.2% and 96.1%, respectively, and were not significantly different among treatments. The 5-year cumulative incidence of overall failure for RT, surgery, IC, and observation was 0%, 9.7% (p = .160), 30.8% (p = .017), and 31.3% (p = .039). There was no grade ≥3 toxicity in RT group according to the CTCAE 5.0 reporting system. Quality of life (QoL) was at similarly good levels among the treatment groups. BALT lymphoma had a favorable prognosis but persistent risk of relapse after IC or observation. Given the very low disease failure risk and good QoL, RT remains an effective initial treatment for BALT lymphoma.

BALT lymphoma has a favorable prognosis but a persistent progression and relapse risk.Radiotherapy is associated with lower failure of disease progression and relapse, low toxicity and good quality of life.

Prediction of 5-year overall survival of diffuse large B-cell lymphoma on the pola-R-CHP regimen based on 2-year event-free survival and progression-free survival.

This study aimed to predict the 5-year overall survival (OS) benefit of pola-R-CHP versus R-CHOP in the POLARIX trial based on the 2-year event-free survival (EFS) and progression-free survival (PFS) rates in diffuse large B-cell lymphoma (DLBCL). We identified randomized controlled trials (RCT) published before 31 May 2023. The correlation between the logarithmic (log) hazard ratio (HR) for EFS (HREFS) or PFS (HRPFS) and the HR for OS (HROS) was estimated at the trial-level. Correlation analysis was performed between 2-year PFS or EFS and 5-year OS rates at the treatment arm-level. Linear regression models were used to calculate the 5-year OS of pola-R-CHP and R-CHOP. In the included 20 RCTs, a linear correlation between HREFS (r = 0.765) or HRPFS (r = 0.534) and HROS was observed at the trial- level. Two-year EFS (r = 0.918) or 2-year PFS (r = 0.865) correlated linearly with 5-year OS. Linear regression analysis between 2-year EFS/PFS and 5-year OS gave estimated 5-year OS rates between pola-R-CHP and R-CHOP of 6.4% and 6.3%, respectively. Two-year EFS and PFS are feasible early endpoints in patients with DLBCL treated primarily with immunochemotherapy. The pola-R-CHP regimen is expected to improve 5-year OS.