Preoperative chemoradiation-induced hematological toxicity and related vertebral dosimetry evaluations in patients with locally advanced gastric cancer: data from a phase III clinical trial.

BACKGROUND: To explore the hematological toxicity (HT) induced by neoadjuvant chemoradiotherapy (nCRT) compared with neoadjuvant chemotherapy (nCT) and to identify the appropriate vertebral body (VB) dosimetric parameters for predicting HT in patients with locally advanced gastric cancer (GC). METHODS: In the phase III study, 302 patients with GC from an ongoing multi-center randomized clinical trial (NCT01815853) were included. Patients from two major centers were grouped into training and external validation cohorts. The nCT group received three cycles of XELOX chemotherapy, while the nCRT received the same dose-reduced chemotherapy plus 45 Gy radiotherapy. The complete blood counts at baseline, during neoadjuvant treatment, and in the preoperative period were compared between the nCT and nCRT groups. The VB was retrospectively contoured and the dose-volume parameters were extracted in the nCRT group. Patients' clinical characteristics, VB dosimetric parameters, and HTs were statistically analyzed. Instances of HT were graded according to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0). The receiver operating characteristic (ROC) curves were generated to identify the optimal cut-off points for dosimetric variables and verify the prediction efficiency of the dosimetric index in both training and external validation cohorts. RESULTS: In the training cohort, 27.4% Grade 3 + HTs were noted in the nCRT group and 16.2% in the nCT group (P = 0.042). A similar result was exhibited in the validation cohort, with 35.0% Grade 3 + HTs in the nCRT group and 13.2% in the nCT group (P = 0.025). The multivariate analysis of the training cohort revealed that V5 was associated with Grade 3 + leukopenia (P = 0.000), Grade 3 + thrombocytopenia (P = 0.001), and Grade 3 + total HTs (P = 0.042). The Spearman correlation analysis identified a significant correlation of V5 with the white blood cell nadir (P = 0.0001) and platelet nadir (P = 0.0002). The ROC curve identified the optimal cut-off points for V5 and showed that V5 < 88.75% could indicate a decreased risk of Grade 3 + leukopenia, thrombocytopenia, and total HTs in the training as well as the external validation cohorts. CONCLUSIONS: Compared with nCT, nCRT could increase the risk of Grade 3 + HT in patients with locally advanced GC. Dose constraints of V5 < 88.75% in irradiated VB could reduce the incidence of Grade 3 + HT.

Neoadjuvant chemoradiotherapy induced lymphopenia in gastric cancer and associations with spleen dosimetry and survival outcomes.

Background: Few studies concentrate on spleen dosimetry of radiotherapy for gastric cancer (GC). Although there is no consensus on the spleen dose-volume threshold for lymphopenia, several studies indicated that the higher the spleen dose, the higher the risk of lymphopenia. This study aimed to identify the appropriate spleen dosimetric parameters for predicting grade 4 + lymphopenia in patients with locally advanced GC. Material and methods: A total of 295 patients treated with nCRT and nChT from June 2013 to December 2021 at two major centers were included, of whom 220 were assigned to the training cohort and 75 to the external validation cohort. Results: Grade 4 + lymphopenia was more common in the nCRT than in the nChT group (49.5% vs. 0, P < 0.001 in the training cohort; 25.0% vs. 0, P = 0.001 in the external validation cohort). Age ≥ 60 years (P = 0.006), lower pretreatment absolute lymphocyte count (P = 0.001), higher spleen volume (SPV) (P = 0.001), and higher V20 (P = 0.003) were significant risk factors of grade 4 + lymphopenia for patients treated with nCRT. Patients with grade 4 + lymphopenia had significantly worse PFS (P = 0.043) and showed a negative correlation trend with OS (P = 0.07). Limiting V20 to < 84.5% could decrease the incidence of grade 4 + lymphopenia by 35.7%. The predictive effectiveness of the multivariable model in the training and external validation cohorts was 0.880 and 0.737, respectively. Conclusion: Grade 4 + lymphopenia during nCRT was more common than nChT, and was associated with a worse PFS in GC patients. Constraining the spleen V20 to < 84.5% may indirectly improve outcomes through lymphocyte preservation.

[Determination of the repair half-time of human nasopharyngeal carcinoma cell lines CNE1, CNE2, HONE1 and C666-1].

OBJECTIVE: To determine the repair half-time (T1/2), a speed parameter of sub-lethal damage repair (SLDR), of human nasopharyngeal carcinoma (NPC) cell lines CNE1, HONE1, C666-1 and CNE2. METHODS: A total radiation dose of 8 Gy divided into 4+4 Gy was delivered to the cell lines at the interval of 0 s, 15 s, 30 s, 1 h, 2 h, 4 h or 6 h. The cell survival fractions were determined using the standard cell clonogenic assay. The curves of the changes in the surviving cell fraction after a total dose of 8 Gy, as a function of the interval between the two doses of 4 Gy, were fitted manually, and the T1/2 of each cell line was calculated according to the curves. RESULTS: The T1/2 of CNE1, HONE1, C666-1 and CNE2 were 18 s, 22 s, 29 s and 27 s, respectively. CONCLUSION: The speed of SLDR of NPC cells is quite rapid, indicating that the fraction delivery time longer than 20 s might decrease the effect of radiotherapy.

[Three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for massive primary liver cancer].

OBJECTIVE: To evaluate the outcomes of patients with unresectable massive primary liver cancer (PLC) receiving three-dimensional conformal radiotherapy (3-DCRT) combined with transcatheter arterial chemoembolization (TACE). METHODS: From January 2001 to December 2004, 84 patients with unresectable massive PLC (tumor size> or =10 cm) received 3-DCRT combined with TACE, including 49 cases in UICC/AJCC T(3) stage and 35 cases in T(4) stages. Lymph node metastasis was found in none of the patients, and portal vein tumor thrombosis (PVTT) was detected in 30 cases. Child-Pugh grade A of liver cirrhosis was present in 64 cases and grade B in 20 cases. The mean value of GTV was 705-/+430 cm(3) (170-2099 cm(3)). Following injections of fluorouracil and hydroxycamptothecine into the target artery of the tumor, the mixture of carboplatin, mitomycin (or pirarubicin) and super-liquefactive iodized oil was injected into the target artery. Gelatin sponge was used to embolize the artery. The procedure was repeated every 1.5-2 months according to the condition of the patients, and each patient received 1-3 such procedures. 3-DCRT was performed in all the patients, who received a total dose of 53.6-/+6.6 Gy (4-6 Gy per fraction at the interval of 48 h), and 3 fractions were given every week. RESULTS: Eight patients died in 3 months after 3-DCRT and were not evaluated. The total response rate (CR+PR) in these patients was 68.9% (51/74). The overall survival rates at 1, 2 and 3 years were 55.4%, 24.7% and 15.4%, respectively. T stage, GTV, PVTT and fraction size had no significant impact on the overall survival. Child-Pugh grade was found to have significant impact on the patients' survival (P=0.035, RR=2.440). CONCLUSION: 3-DCRT combined with TACE has definite therapeutic effect on advanced massive PLC, and Child-Pugh grade is an independent prognostic factor in such cases.