Chemoradiotherapy Versus Chemotherapy Alone for Advanced Esophageal Squamous Cell Carcinoma: The Role of Definitive Radiotherapy for Primary Tumor in the Metastatic Setting.

Introduction: The role of definitive radiotherapy in advanced esophageal squamous cell carcinoma (ESCC), especially in the metastatic setting, remains unclear. Therefore, we aimed to investigate the efficacy of chemoradiotherapy (CRT) versus chemotherapy (CT) alone in these selected patients. Methods: We retrospectively evaluated 194 newly diagnosed advanced ESCC who underwent definitive CRT or CT alone, including 97 patients with locally advanced and 97 patients with distant metastatic disease. Cumulative overall survival (OS) and progression-free survival (PFS) were evaluated with a log-rank test. Propensity score matching was used to simulate random allocation. In addition, we performed subgroup analysis in the locally advanced and metastatic disease. Results: After matching, 63 well-paired patients were selected. The adjusted median OS (12.5 vs. 7.6 months, p = 0.002) and PFS (9.0 vs. 4.8 months, p = 0.0025) in the CRT group were superior to that in the CT-alone group. Further subgroup analysis revealed that CRT conferred survival benefits to both locally advanced and metastatic cohorts. For patients with distant metastasis, median OS (12.9 vs. 9.3 months, p = 0.029) and PFS (9.9 vs. 4.0 months, p =0.0032) in the CRT group were superior to that in the CT-alone group. In a multivariate Cox regression analysis of the entire cohort, additional definitive radiotherapy was independently associated with better OS (p = 0.041) and PFS (p = 0.007). Conclusions: In both locally advanced and metastatic ESCC, additional definitive-dose radiotherapy was associated with improved clinical outcomes. Therefore, more consideration should be given to its application in the metastatic setting.

Impact of Cold Weather on Setup Errors in Radiotherapy.

Objective: To investigate the influence of cold weather on setup errors of patients with chest and pelvic disease in radiotherapy. Methods: The image-guided data of the patients were collected from the Radiotherapy Center of Cancer Hospital Affiliated to Guangxi Medical University from October 2020 to February 2021. During this period, the cold weather days were December 15, 16, and 17, 2020, and January 7 and 8, 2021. For body fixation in radiotherapy, an integrated plate and a thermoplastic mold were employed in 18 patients with chest disease, while an integrated plate and a vacuum pad were applied in 19 patients with pelvic disease. All patients underwent cone beam computed tomography (CBCT) scans in the first five treatments and once a week thereafter. The obtained data were registered to the planning CT image to get the setup errors of the patient in the translational direction including X, Y, and Z axes and rotational direction including R X , R Y , and R Z . Then, the Mann-Whitney U test was performed. The expansion boundary values of the chest and pelvis were calculated according to the formula M PTV=2.5∑+0.7δ. Results: A total of 286 eligible results of CBCT scans were collected. There were 138 chest CBCT scans, including 26 taken in cold weather and 112 in usual weather, and 148 pelvic CBCT scans, including 33 taken in cold weather and 115 in usual weather. The X-, Y-, and Z-axis translational setup errors of patients with chest disease in the cold weather group were 0.16 (0.06, 0.32) cm, 0.25 (0.17, 0.52) cm, and 0.35 (0.21, 0.47) cm, respectively, and those in the usual weather group were 0.14 (0.08, 0.29) cm, 0.23 (0.13, 0.37) cm, and 0.18 (0.1, 0.35) cm, respectively. The results indicated that there was a statistical difference in the Z-axis translational error between the cold weather group and the usual weather group (U = 935.5; p=0.005 < 0.05), while there was no statistical difference in the rotational error between the two groups. The external boundary values of X, Y, and Z axes in the cold weather group were 0.57 cm, 0.92 cm, and 0.99 cm, respectively, and those in the usual weather group were 0.57 cm, 0.78 cm, and 0.68 cm, respectively. There was no significant difference in the translational and rotational errors of patients with pelvic disease between the cold weather group and the usual weather group (p < 0.05). The external boundary values of X, Y, and Z axes were 0.63 cm, 0.79 cm, and 0.68 cm in the cold weather group and 0.61 cm, 0.79 cm, and 0.61 cm in the usual weather group, respectively. Conclusion: The setup error of patients undergoing radiotherapy with their bodies fixed by an integrated plate and a thermoplastic mold was greater in cold weather than in usual weather, especially in the ventrodorsal direction.

Comparison of graphical optimization or IPSA for improving brachytheraphy plans associated with inadequate target coverage for cervical cancer.

Many studies have reported that inverse planning by simulated annealing (IPSA) can improve the quality of brachytherapy plans, and we wanted to examine whether IPSA could improve cervical cancer brachytherapy plans giving D90 < 6 Gy (with 7 Gy per fraction) at our institution. Various IPSA plans involving the tandem and ovoid applicators were developed for 30 consecutive cervical cancer patients on the basis of computed tomography: IPSA1, with a constraint on the maximum dose in the target volume; IPSA1-0, identical to IPSA1 but without a dwell-time deviation constraint; IPSA2, without a constraint on the maximum dose; and IPSA2-0, identical to IPSA2 but without a dwell-time deviation constraint. IPSA2 achieved similar results as graphical optimization, and none of the other IPSA plans was significantly better than graphical optimization. Therefore, other approaches, such as combining interstitial and intracavitary brachytherapy, may be more appropriate for improving the quality of brachytherapy plans associated with inadequate target coverage.

Therapeutic efficacy of tumor-derived heat shock protein 70 immunotherapy combining interleukin-2 on tumor-bearing mice.

OBJECTIVE: To investigate the therapeutic efficacy of compound immunotherapy of tumor-derived heat shock protein 70 (HSP70) and interleukin-2 (IL-2) on tumor-bearing mice, and to provide reference for translating this strategy to human cancer. METHODS: Cell culture, techniques for protein extraction and purification, SDS-PAGE, Western blot and capillary electrophoresis for HSP70 detection and purity analysis, and animal experiments were used. Mice were treated with HSP70 5 or 10 microg and IL-2 50 kU, 100 kU or 2 kU (maintaining dosage) at previously designated intervals. RESULTS: Both the mono-administration of either HSP70 or IL-2 and the compound immunotherapy of HSP70 and IL-2 obviously inhibited the growth of the implanted tumor and prolonged the life span of the mice to different extents. However, long periods of tumor-free survival (over 90 days) were demonstrated only in HSP70 10 micro g group, HSP70 10 microg-IL-2 50 kU group, and HSP70 10 microg-IL-2 100 kU group (40%, 40%, 60% respectively). On the other hand, none of the mice in the rest groups achieved long-term survival. Statistical significance was apparent in comparison with the groups without long period survival (P < 0.025 - 0.05). CONCLUSION: Our research revealed that tumor-derived HSP70 immunotherapy was much more effective than IL-2 alone. And in compound immunotherapy, HSP70 was the main factor in delaying or eradicating the tumors. The proper combination of HSP70 and IL-2 (10 microg HSP70 and 100 kU IL-2 in this experimental mouse model) clearly enhanced the immunotherapy efficacy which indicated that the specific immunotherapy as a main part of tumor immunotherapy assisted by cytokine immunotherapy would be a promising strategy in cancer treatment.

[The therapeutic efficacy of tumor-derived heat shock protein70 combining interleukin-2 on tumor-bearing mice].

AIM: To investigate the therapeutic efficacy of the combination of tumor-derived HSP70 and IL-2 on tumor-bearing mice. METHODS: HSP70 was purified from the murine tumor cell line by liquid chromatography. And then identified by SDS-PAGE and Western blot,the purity of purified product was analyzed by capillary electrophoresis. The anti-tumor efficacies of mono-administration of HSP70 or IL-2 and their combination were observed by zoopery. RESULTS: Combination of HSP70 and IL-2 was more effective than either of the two therapeutic agents alone in treating tumor-bearing mice. 10 microg HSP70 displayed obviously therapeutic effect no matter applied alone or combined with IL-2. The averaged life span of the mice treated with IL-2 was only 36.6+/-13.0 days, while 40% of the mice treated with 10 microg HSP70, tumors disappeared eventually and their survival time was more than 90 days, and the averaged life span of this group was over 59.2+/-29.6 days. HSP70 plus IL-2 could get tumors disappeared completely in 60% of mice, averaged life time of this group was over 70.8+/-26.5 days. CONCLUSION: The Combination of HSP70 and IL-2 demonstrated apparently therapeutic effect on tumor-bearing mice. The results will be of greater value to the study on the immunotherapy of human malignant tumors.

Efficacy of intraperitoneal thermochemotherapy and immunotherapy in intraperitoneal recurrence after gastrointestinal cancer resection.

AIM: To investigate the prophylactic and therapeutic efficacy of intraperitoneal IL-2 immunotherapy following intraperitoneal thermochemotherapy in the metastasis and recurrence of gastric and colorectal cancer after operation. METHODS: Forty-two gastric cancer patients at T(3)II-T(4)III( B) stages and 96 patients with colorectal cancer at B to D stages admitted from January 1996 to October 1998 were randomly divided into control group (group I, 65 cases) receiving intraperitoneal thermochemotherapy, and group II (73 cases) receiving both intraperitoneal thermochemotherapy and intraperitoneal IL-2 immunotherapy. Distilled water at 43-45 degrees containing 5-Fu 0.5 g/L and MMC 8 mg/L was perfused into peritoneal cavity before closure at the end of operation for 1 h, and from the third day, IL-2 10 million IU in 500 ml 0.9 % sodium chloride was intraperitoneally administrated daily for 10 times. One month after operation, all the patients underwent regular intravenous chemotherapy. Before and after the IL-2 immunotherapy, some Th1 type cytokines in the peripheral blood of the patients in the two groups were detected by ELISA, and the intraperitoneal recurrence and liver metastasis rates and the 3-year survival rate were statistically evaluated after intensive follow-up. RESULTS: IL-2 intraperitoneal immunotherapy significantly elevated the level of some Th1 type cytokines (P<0.01 compared with that of control group), and the 3-year survival rate of group II was 18.1 % higher and the rates of intraperitoneal recurrence and liver metastasis were 16.9 % and 6.0 % lower than those of group I significantly (P<0.05-0.01). CONCLUSION: The combination of intraperitoneal IL-2 immunotherapy and thermochemotherapy could promote Th1 immune paradigm and enforce anti-tumor activity of bodies, which plays a positive role in preventing gastric and colorectal cancer from intraperitoneal recurrence and development.

Study on the anti-tumor efficacy induced by heat shock protein 70-peptide complexes derived from tumor cells.

OBJECTIVE: To study the efficacy and explore the mechanism of the anti-tumor immunity elicited by heat shock protein 70-peptide complexes (HSP70-PC) derived from tumor cells. METHODS: Cells culture, flow cytometric analysis, affinity chromatography for protein purification, SDS-PAGE, Western-blotting and animal experiment were used. RESULTS: HSP70-PC immunization rendered protective effect to both naive tumorl-bearing mice. All of the naive mice obtained complete resistance to Hcaf cell attack; 40% of the tumor-bearing mice survived for over 90 days, whereas the mice of control group died within 2 weeks (P < 0.01). CD8+ subset of T lymphocytes in the peripheral blood of immunized mice increased by 12%. CONCLUSION: HSP70-PC induces anti-tumor immunity via activation of cytotoxic T lymphocytes (CTLs), and it possesses strong tumor vaccine effect. Our research adds more evidence to support the clinical use of HSP70-PC to fight human cancers.