Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To analyze the efficacy and prognostic factors of fractionated stereotactic radiotherapy (FSRT) for patients with breast cancer brain metastases (BCBM).Methods:Medical records and follow-up data of BCBM patients who underwent FSRT in Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center and Shenzhen People's Hospital from August 2019 to May 2023 were collected. The R Studio platform of the R version 4.2.1 statistical software was applied to analyze patients' baseline characteristics, 1- and 2-year local brain control (LBC), overall survival (OS) and distant brain control (DBC) and corresponding median failure-free survival, draw survival curve using Kaplan-Meier method. Prognostic factors were screened by univariate analysis and multivariate analysis (Cox regression).Results:Cumulatively, 52 patients (163 metastases in total) had a median survival follow-up of 22.1 months, 83% were<60 years old. Molecular typing: 13 cases (25%) were positive for human epidermal growth factor receptor 2 (HER2+) / hormone receptor negative (HR-), 2 cases (4%) were luminal A, 26 cases (50%) were luminal B, and 11 cases (21%) were triple negative. The median number of brain metastases was 2 (range: 1 - 17). Follow-up outcomes: the median OS was 34.0 months, with 1- and 2-year OS rates of 85.6% and 65.4%, respectively; the median LBC was 20.6 months, with 1- and 2-year LBC rates of 79.2% and 45.2%, respectively; and the median DBC was 10.3 months, with 1- and 2-year DBC rates of 46.7% and 28.9%, respectively. During follow-up, 13 patients underwent salvage local therapy (10 FSRT); 5 developed radiation necrosis (1 symptomatic). Prognostic factor analysis: absence of extracranial organ metastases (compared with ≥3) was a protective factor for OS, P<0.05. For LBC, fewer (1 - 2) extracranial organ metastases (compared with ≥3), and single brain metastasis (compared with ≥2) were favorable prognostic factors , while N 3 staging upon initial diagnosis was a poor prognostic factor (all P<0.05). For DBC, brain metastasis after surgery was a good prognostic factor, while complicated with lung metastasis and asymptomatic brain metastasis at the first diagnosis were poor prognostic factors (all P<0.05). Conclusions:FSRT yields relatively good LBC and poor DBC for BCBM patients. A certain percentage of patients require salvage FSRT during follow-up, but OS is maintained acceptable and the radiation necrosis is tolerable. Among the prognostic factors, the absence of extracranial metastatic organs is a good prognostic factor for OS; patients with single brain metastasis, fewer extracranial metastatic organs, and non-N 3 staging upon initial diagnosis can obtain better LBC after FSRT.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To analyze the efficacy and prognostic factors of fractionated stereotactic radiotherapy (FSRT) for patients with breast cancer brain metastases (BCBM).Methods:Medical records and follow-up data of BCBM patients who underwent FSRT in Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center and Shenzhen People's Hospital from August 2019 to May 2023 were collected. The R Studio platform of the R version 4.2.1 statistical software was applied to analyze patients' baseline characteristics, 1- and 2-year local brain control (LBC), overall survival (OS) and distant brain control (DBC) and corresponding median failure-free survival, draw survival curve using Kaplan-Meier method. Prognostic factors were screened by univariate analysis and multivariate analysis (Cox regression).Results:Cumulatively, 52 patients (163 metastases in total) had a median survival follow-up of 22.1 months, 83% were<60 years old. Molecular typing: 13 cases (25%) were positive for human epidermal growth factor receptor 2 (HER2+) / hormone receptor negative (HR-), 2 cases (4%) were luminal A, 26 cases (50%) were luminal B, and 11 cases (21%) were triple negative. The median number of brain metastases was 2 (range: 1 - 17). Follow-up outcomes: the median OS was 34.0 months, with 1- and 2-year OS rates of 85.6% and 65.4%, respectively; the median LBC was 20.6 months, with 1- and 2-year LBC rates of 79.2% and 45.2%, respectively; and the median DBC was 10.3 months, with 1- and 2-year DBC rates of 46.7% and 28.9%, respectively. During follow-up, 13 patients underwent salvage local therapy (10 FSRT); 5 developed radiation necrosis (1 symptomatic). Prognostic factor analysis: absence of extracranial organ metastases (compared with ≥3) was a protective factor for OS, P<0.05. For LBC, fewer (1 - 2) extracranial organ metastases (compared with ≥3), and single brain metastasis (compared with ≥2) were favorable prognostic factors , while N 3 staging upon initial diagnosis was a poor prognostic factor (all P<0.05). For DBC, brain metastasis after surgery was a good prognostic factor, while complicated with lung metastasis and asymptomatic brain metastasis at the first diagnosis were poor prognostic factors (all P<0.05). Conclusions:FSRT yields relatively good LBC and poor DBC for BCBM patients. A certain percentage of patients require salvage FSRT during follow-up, but OS is maintained acceptable and the radiation necrosis is tolerable. Among the prognostic factors, the absence of extracranial metastatic organs is a good prognostic factor for OS; patients with single brain metastasis, fewer extracranial metastatic organs, and non-N 3 staging upon initial diagnosis can obtain better LBC after FSRT.

Lung cancer is the malignant tumor with the highest mortality in the world, of which non-small cell lung cancer (NSCLC) accounts for about 80%. The orderly combination of surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy is currently the main treatment modality for NSCLC. Liquid biopsy has been increasingly used in clinical practice in recent years due to its advantages of being non-invasive and overcoming tumor heterogeneity, of which circulating tumor DNA (ctDNA) is one of the most commonly used analytical indicators, and ctDNA detection may play a role in the treatment of NSCLC. This article reviews new developments in the use of ctDNA for prognostic assessment, recurrence monitoring and efficacy prediction in NSCLC patients.

Objective To compare target dosimetric distribution and normal tissue radiation between different static intensity-modulated radiation therapy (IMRT)plans and volumetric modulated arc therapy (VMAT),and to identify the best IMRT plan for lymphoma patients needed mediastinal radiation. Methods A total of 11 patients with lymphoma who received first course radiotherapy in the mediastinal region after che-motherapy in Cancer Hospital & Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College from March 2017 to January 2019 were included in the study. There were 8 males and 3 fe-males,2 patients were in Ann Arbor stage Ⅰ-Ⅱ,and 9 cases in Ⅲ-Ⅳ stage. There were 6 patients with Hodgkin lymphoma (HL)and 5 patients with non-Hodgkin lymphoma (NHL). Patients with HL and NHL were given prescript doses of 36 Gy and 50 Gy,respectively. Three plans were designed for each patient:static 5F-IMRT,7F-IMRT and VMAT plan. The target dosimetric distribution,normal tissue radiation dose,and effi-ciency of each plan were evaluated. Results The mean conformity index (CI)and homogeneity index (HI) values of plan target volume (PTV)in 5F-IMRT,7F-IMRT,VMAT plan were 0. 64 ± 0. 06,0. 67 ± 0. 05, 0. 76 ± 0. 04 (F = 17. 045,P < 0. 001)and 1. 07 ± 0. 01,1. 07 ± 0. 01,1. 09 ± 0. 01 (F = 9. 258,P =0. 001),respectively. VMAT showed significantly better CI than two static IMRT plans (both P < 0. 001),but worse HI (both P < 0. 001). The lungs low dose irradiation volume (V (V 5 )and high dose irradiation volume 30 )in 5F-IMRT,7F-IMRT,VMAT plan were (43. 98 ± 7. 77)％,(42. 71 ± 4. 98)％,(55. 92 ± 8. 16)％(F = 8. 281,P = 0. 001)and (8. 19 ± 2. 97)％,(8. 25 ± 2. 87)％,(7. 53 ± 3. 16)％ (F = 0. 140,P =0. 870),respectively. The volume of low dose irradiation in lungs of VMAT plan was significantly higher than 5F-IMRT and 7F-IMRT plans (both P < 0. 001),while high dose volume was no significant difference. The left and right breast low dose irradiation volume (V 4 )in 5F-IMRT,7F-IMRT and VMAT plan were (24. 29 ± 8. 14)％,(23. 87 ± 7. 70)％,(80. 17 ± 22. 92)％ (F = 14. 505,P = 0. 005)and (22. 12 ± 13. 28)％, (21. 13 ± 13. 01)％,(81. 77 ± 20. 76)％ (F = 13. 938,P = 0. 006),respectively. VMAT showed signifi-cantly higher breast low dose irradiation volume than static IMRT plan (both P < 0. 05). The number of monitor units and treatment time in 5F-IMRT,7F-IMRT,VMAT plan were (1622 ± 281)MU,(1729 ± 286)MU, (411 ± 75)MU (F = 105. 277,P < 0. 001)and (6. 79 ± 0. 93)min,(7. 42 ± 0. 95)min,(4. 98 ± 0. 00)min (F = 29. 545,P < 0. 001),respectively. VMAT showed significantly less monitor units than static IMRT (both P < 0. 001)and shorter treatment time (both P < 0. 001). Conclusion For lymphoma patients who have the indication of mediastinal radiotherapy,VMAT is highly efficient and has no definite dose advan-tage,the static 5F-IMRT or 7F-IMRT plan has good conformal and uniform target area,and some organs at risk exposure is even lower.

OBJECTIVETo explore the impact of AJCC TNM Staging 7th edition on survival outcome of limited stage small cell lung cancer (SCLC).

METHODSFour hundred and thirty-seven SCLC patients with completed diagnosis and treatment data treated in our department between January 1996 and December 2006 were reclassified according to the AJCC TNM Staging 7th edition. The patients of stages IA, IB, IIA, IIB, IIIA, IIIB were 8, 44, 7, 64, 192 cases, respectively. Kaplan-Meier method was used for survival analysis and log-rank test was used to identify the prognostic factors. The survival rate was determined using chi-square test.

RESULTSThe median follow-up time was 64 months. The median survival time was 26.2 months and median progression free survival time was 13.7 months. The 1-, 2- and 5-year overall survival rates were 86.0%, 52.7%, and 29.7%, respectively. The log-rank test showed that TNM stage is a statistically significant prognostic factor for OS in LS-SCLC (P<0.001). TNM staging system generally allowed a good separation in pairwise comparison for OS between successive stages except there was no significant difference between stages I and II (P=0.061). The 5-year progression free survival rates of patients of stage I, II, IIIA and IIIB were 53.2%, 43.2%, 16.8%, and 10.9%, respectively. TNM stage also was a statistically significant prognostic factor for PFS in LS-SCLC (P<0.001), but there was no significant difference between successive stages (P>0.05 for all). The T staging confirmed significant influence on OS (P<0.001) with no significant difference between successive stages (P>0.05 for all), while T stage was not a significant prognostic factor for PFS in the LS-SCLC patients (P=0.194). N stage also had a significant influence on OS (P<0.001), but with no significant differences between successive stages except N1 and N2 (P=0.001). N staging also showed significant influence on PFS (P=0.001), but with no significant difference between successive stages (P>0.05) except that between the 5-year survival rates of N2 and N3 cases (P=0.013). The cumulative brain metastasis rates of stages I, II, IIIA, and stage IIIB were 17.3%, 28.6%, 33.3%, and 35.8%, respectively(P=0.072), and were 12.8% and 30.8% for pathological stage I and clinical stage I (P=0.203).

CONCLUSIONAJCC TNM Staging 7th edition criteria for LS-SCLC patients have a high prognostic impact and therefore are preferable in clinical practice and future therapeutic trials.

Disease Progression ; Disease-Free Survival ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms ; mortality ; pathology ; Neoplasm Staging ; methods ; Prognosis ; Retrospective Studies ; Small Cell Lung Carcinoma ; mortality ; pathology ; Survival Analysis ; Survival Rate ; Time Factors

OBJECTIVETo evaluate the effect of comprehensive treatment and examine the impact of clinical factors on the survival outcome of limited-stage small cell lung cancer.

METHODSThe clinical records of 335 patients with limited-stage small cell lung cancer treated in the Cancer Hospital of Chinese Academy of Medical Sciences between January 1996 and December 2006 were analyzed retrospectively in this study. Kaplan-Meier method was used for survival analysis, and log-rank test and Cox regression were used for univariate and multivariate analyses of prognostic factors.

RESULTSThe median follow-up time was 54 months for all patients, the median survival time was 23.8 months, and progression-free survival was 12.5 months. The 2-, 3-, and 5-year overall survival rates were 47.3%, 32.9%, and 22.9%, respectively. The acute toxicity during comprehensive treatment was tolerable. The incidence of ≥grade 3 hematological toxicity, ≥grade 3 gastrointestinal toxicity, ≥grade 2 radiation pneumonitis and ≥grade 2 acute esophagitis were 37.0%, 14.9%, 11.0%, and 38.8%, respectively. The univariate analysis showed that KPS<80, smoking and high LDH level significantly reduced the overall survival time in patients with limited-stage SCLC. The multivariate analysis showed that KPS and weight loss were independent factors affecting the prognosis for the limited stage SCLC patients (P<0.05 for all).

CONCLUSIONSSequential chemoradiotherapy can be safely and effectively performed in limited-stage small cell lung cancer. Krnofsky performance status and weight loss are independent prognostic factors for the overall survival of LS-SCLC.

Chemoradiotherapy ; Disease-Free Survival ; Esophagitis ; Humans ; Lung Neoplasms ; diagnosis ; epidemiology ; pathology ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Small Cell Lung Carcinoma ; diagnosis ; epidemiology ; pathology ; Survival Analysis ; Survival Rate

Objective To evaluate the effect of comprehensive treatment and examine the impact of clinical factors on the survival outcome of limited-stage small cell lung cancer.Methods The clinical records of 335 patients with limited-stage small cell lung cancer treated in the Cancer Hospital of Chinese Academy of Medical Sciences between January 1996 and December 2006 were analyzed retrospectively in this study.Kaplan-Meier method was used for survival analysis, and log-rank test and Cox regression were used for univariate and multivariate analyses of prognostic factors.Results The median follow-up time was 54 months for all patients, the median survival time was 23.8 months, and progression-free survival was 12.5 months.The 2-,3-, and 5-year overall survival rates were 47.3%, 32.9%, and 22.9%, respectively. The acute toxicity during comprehensive treatment was tolerable.The incidence of ≥grade 3 hematological toxicity,≥grade 3 gastrointestinal toxicity,≥grade 2 radiation pneumonitis and≥grade 2 acute esophagitis were 37.0%, 14.9%, 11.0%, and 38.8%, respectively.The univariate analysis showed that KPS<80, smoking and high LDH level significantly reduced the overall survival time in patients with limited-stage SCLC.The multivariate analysis showed that KPS and weight loss were independent factors affecting the prognosis for the limited stage SCLC patients ( P <0.05 for all ). Conclusions Sequential chemoradiotherapy can be safely and effectively performed in limited-stage small cell lung cancer.Krnofsky performance status and weight loss are independent prognostic factors for the overall survival of LS-SCLC.

Objective To evaluate the effect of comprehensive treatment and examine the impact of clinical factors on the survival outcome of limited-stage small cell lung cancer.Methods The clinical records of 335 patients with limited-stage small cell lung cancer treated in the Cancer Hospital of Chinese Academy of Medical Sciences between January 1996 and December 2006 were analyzed retrospectively in this study.Kaplan-Meier method was used for survival analysis, and log-rank test and Cox regression were used for univariate and multivariate analyses of prognostic factors.Results The median follow-up time was 54 months for all patients, the median survival time was 23.8 months, and progression-free survival was 12.5 months.The 2-,3-, and 5-year overall survival rates were 47.3%, 32.9%, and 22.9%, respectively. The acute toxicity during comprehensive treatment was tolerable.The incidence of ≥grade 3 hematological toxicity,≥grade 3 gastrointestinal toxicity,≥grade 2 radiation pneumonitis and≥grade 2 acute esophagitis were 37.0%, 14.9%, 11.0%, and 38.8%, respectively.The univariate analysis showed that KPS<80, smoking and high LDH level significantly reduced the overall survival time in patients with limited-stage SCLC.The multivariate analysis showed that KPS and weight loss were independent factors affecting the prognosis for the limited stage SCLC patients ( P <0.05 for all ). Conclusions Sequential chemoradiotherapy can be safely and effectively performed in limited-stage small cell lung cancer.Krnofsky performance status and weight loss are independent prognostic factors for the overall survival of LS-SCLC.