Neoadjuvant hyperfractionated accelerated radiotherapy plus concomitant 5-fluorouracil infusion in locally advanced rectal cancer: A phase Ⅱ study

AIM To evaluate the efficacy and tolerability of neoadjuvant hyperfractionated accelerated radiotherapy(HART)and concurrent chemotherapy in patients with locally advanced infraperitoneal rectal cancer. METHODS A total of 30 patients with histopathologically confirmed T2-3/N0+ infraperitoneal adenocarcinoma of rectum cancer patients received preoperative 42 Gy/1.5 Gy/18 days/bid radiotherapy and continuous infusion of 5-fluorouracil(325 mg/m^2). All patients were operated 4-8 wk after neoadjuvant concomitant therapy. RESULTS In the early phase of treatment, 6 patients had grade Ⅲ-Ⅳ gastrointestinal toxicity, 2 patients had grade Ⅲ-Ⅳ hematologic toxicity, and 1 patient had grade Ⅴ toxicity due to postoperative sepsis during chemotherapy. Only 1 patient had radiotherapy-related late side effects, i.e., grade Ⅳ tenesmus. Complete pathological response was achieved in 6 patients(21%), while near-complete pathological response was obtained in 9(31%). After a median follow-up period of 60 mo, the local tumor control rate was 96.6%. In 13 patients, distant metastasis occurred. Disease-free survival rates at 2 and 5 years were 63.3% and 53%, and corresponding overall survival rates were 70% and 53.1%, respectively.CONCLUSION Although it has excellent local control and complete pathological response rates, neoadjuvant HART concurrent chemotherapy appears to not be a feasible treatment regimen in locally advanced rectal cancer, having high perioperative complication and intolerable side effects. Effects of reduced 5-fluorouracil dose or omission of chemotherapy with the aim of reducing toxicity may be examined in further studies.

Is there a place for optimizing thoracic radiotherapy in limited-stage small cell lung cancer after twenty years?

Thoracic radiotherapy(TRT)is one of the main treatments in limited-stage small cell lung cancer(LS-SCLC).Hyperfractionated TRT(45 Gy,1.5 Gy twice daily)has been the standard of care(SOC)since Turrisi and colleagues published the results of their clinical trial in 1999.Two meta-analyses have demonstrated the benefits of concurrent chemotherapy and TRT in terms of intrathoracic disease control at 2 years and 3-year overall survival(OS).The phase 2 trial by Grønberg et al(2016)comparing once-daily hypofractionated TRT to twice-daily hyperfractionated TRT in LS-SCLC found similar outcomes in both groups in terms of response rate,progression-free survival(PFS),grade 3-4 adverse effects,and OS.The CONVERT trial,published in 2017,failed to demonstrate the superiority of the conventional scheme(once-daily TRT)vs twice-daily radiotherapy,despite the application of modern radiotherapy techniques and a quality assurance programme,thus confirming the twice-daily hyperfractionated regimen as the SOC.At the 2020 American Society of Clinical Oncology(ASCO)annual meeting,Grønberg et al reported preliminary findings from a phase 2 trial comparing two different TRT dose regimens(45 Gy vs 60 Gy),both administered twice daily.Those data demonstrated a marked improvement in 2-year survival rates in the high dose arm(70.2%vs 46.1%,P=0.002),despite similar objective response rates and PFS outcomes.Those findings provide a new treatment alternative to consider:Hyperfractionated,high-dose TRT.However,the results of that trial will need to be validated in a large,randomized phase 3 study.The results of the phase 2 CALCG 30610 trial will help to clarify the optimal dose and regimen.The potential role of upfront immunotherapy,which early data suggest may improve OS,also needs to be determined.

GOECP/SEOR radiotherapy guidelines for small-cell lung cancer

Small cell lung cancer(SCLC)accounts for approximately 20%of all lung cancers.The main treatment is chemotherapy(Ch).However,the addition of radiotherapy significantly improves overall survival(OS)in patients with non-metastatic SCLC and in those with metastatic SCLC who respond to Ch.Prophylactic cranial irradiation reduces the risk of brain metastases and improves OS in both metastatic and non-metastatic patients.The 5-year OS rate in patients with limited-stage disease(non-metastatic)is slightly higher than 30%,but less than 5%in patients with extensive-stage disease(metastatic).The present clinical guidelines were developed by Spanish radiation oncologists on behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Society of Radiation Oncology to provide a current review of the diagnosis,planning,and treatment of SCLC.These guidelines emphasise treatment fields,radiation techniques,fractionation,concomitant treatment,and the optimal timing of Ch and radiotherapy.Finally,we discuss the main indications for reirradiation in local recurrence.

CLINICAL STUDY IN ACCELERATED HYPERFRACTIONATED IRRADIATION IN THE TREATMENT OF LOCAL ADVANCED NON-SMALL CELL LUNG CANCER

Objective To evaluate the effect of accelerated hyperfractionated irradiation (AHFJ) and conventional fractionated irradiation (CFI) for local advanced non- small cell lung cancer (NSCLC). Methods The patients of AI-IFJ group were irradiated to large-field target volume by a daily fraction of 2Gy, and small-field target volume by a daily fraction of 1Gy with more than 6h interval. The total dose of large-field target volume was SOGy/25Fx/SW and of small-field target volume was 7SGy/SOFx/5W. The patients in CFI group were irradiated by a daily fraction of 2Gy to the total dose of 66Gy/33Fx/6. 6W. After 3 months of radiotherapy, the tumor response rates of complete recovery (CR), partial recovery (PR), and no change (NC) and 1- and 2- year survival rate in the two groups were observed. Results The tumor response rates of CR,PR,NC in AHFI group and CFI group were 22.9%(8/35), 60.0%(21/35), 17.1%(6/35) and 11.4% (4/35), 51.4% (18/35), 37.2% (13/35) respectively (P>0. 05). All patients were followed up 2 years or more. The 1- and 2- year survival rates in AHFI group and CFI group were 62.9% (22/35), 31 .4% (11/35) and 42.9% (15/35) , 17.1% (6/35) respectively (P< 0.05). The incidences of esophagitis and pneumonitis in AHFI group and CFI group were 34.3% (12/35), 22. 9% (8/35) and 40.0% (14/35), 17.1% (6/35)(P>0. 05). Conclusion In comparison with CFI, AHFI may increase 1- and 2- year sur-vival rate after treatment of local advanced non-small cell lung cancer, while the radio-reactions, either early or late, did not increase significantly.