BACKGROUND: The aim of this phase 2 study was to determine the long‐term local control, survival, and late toxicities among patients with locally advanced nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiation therapy (SMART) boost technique and concurrent chemotherapy.METHODS: Eighty‐one patients with pathologically diagnosed locally advanced NPC were enrolled in this study. IMRT was delivered with the SMART boost technique at prescribed doses of 68 grays (Gy)/30 fraction to the nasopharynx gross target volume. Concurrent cisplatin chemotherapy (80 mg/m²/d on Days 1 and 22) was administered.RESULTS: The mean actual physical dose delivered to the nasopharynx gross target volume was 73.8 Gy, and the mean biologically effective dose (BED) for the nasopharynx gross target volume was 84.8 Gy. With a median follow‐up of 54 months, 4 (4.9%) patients experienced local recurrence. The 5‐year local control rate was 94.9%. Eighteen patients died. Among them, 66.7% died of distant metastasis. The 5‐year disease‐free and overall survivals were 76.7% and 74.5%, respectively. The most common late toxicities among 68 patients with ≥4 years follow‐up were grade 1‐2 xerostomia, hearing loss, skin dystrophy, and subcutaneous fibrosis. No grade 4 late toxicities were noted.CONCLUSIONS: IMRT with SMART to enhance BED and concurrent chemotherapy is feasible in patients with locally advanced NPC. Long‐term results showed excellent local control with fewer late toxicities, although no further improvement was noted in overall survival, and the major cause of death was distant metastasis. Exploration of more effective combined chemoradiation strategies is warranted. Cancer 2011. © 2010 American Cancer Society.

Objective & Background Total neoadjuvant therapy (TNT) is a novel approach for locally advanced rectal cancer (LARC), which attempts to deliver both systemic chemotherapy and neoadjuvant chemoradiotherapy prior to surgery. However, its efficacy and safety remain controversial in randomized controlled trials (RCTs). We conducted this meta‐analysis to assess such concerns. Methods Head‐to‐head phase II/III RCTs were searched in Embase, PubMed, Web of Science and the Cochrane Library, as well as other sources. The primary endpoint was pathologic complete response (pCR). Secondary endpoints were disease‐free survival (DFS), overall survival (OS), local recurrence‐free survival (LRFS), distant metastasis‐free survival (DMFS) and the R0 resection rate. Results Eight phase II/III RCTs involving 2,196 LARC patients were assessed. The primary analysis demonstrated a statistically significant improvement in the pCR rate for TNT treatment (OR = 1.77, 95% CI: 1.28 to 2.45, P = 0.0005). TNT treatment also showed improvements in DFS and OS outcomes compared with standard CRT (HR=0.83, 95% CI: 0.72 to 0.96, P = 0.03; HR=0.88, 95% CI:0.74 to 1.05, P = 0.15). In addition, TNT treatment showed significant efficacy in reducing the risk of distant metastasis (HR=0.81, 95% CI: 0.68 to 0.95, P = 0.012). Conclusion The overall pCR rate may be improved with TNT compared with standard treatment. The TNT strategy may also improve DFS and OS, and reduce the risk of distant metastasis. Implications for Practice Locally advanced rectal cancer (LARC) is a relatively common disease, with a poor prognosis due to its high metastatic potential. The role of total neoadjuvant therapy (TNT) has always been controversial. This meta‐analysis found that TNT in LARC is associated with a significant improvement in overall pCR rate, DFS, OS, and DMFS compared with standard treatment. TNT is a promising strategy for LARC, especially for patients who have little desire for surgery.

Objective: To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia (MRF). Background Data: nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower-risk LARC patients with uninvolved MRF. Methods: Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to nCT group with 4 cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported the results of secondary end points: histopathologic response, surgical events, and toxicity. Results: Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathologic complete response rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm (P=0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm (P=0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P=0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P=0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a nonsurgical approach. Similar results were observed in subgroup analysis. Conclusions: nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.

The objective of this study is to analyse the factors affecting late toxicity for nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). Seven hundred and eighty-nine consecutive NPC patients treated with IMRT at our centre from January 2003 to February 2008 were retrospectively analysed. Radiotherapy-related complications were categorised using the RTOG Late Radiation Morbidity Scoring Criteria and the Common Terminology Criteria for Adverse Events (Version 3.0). Two hundred and thirty-three patients were treated with IMRT alone (group 1) and 556 patients underwent cisplatin-based chemotherapy (group 2). Median follow-up was 65 months (range, 4–106 months). The 5-year major late toxicity rate was significantly greater in group 2 than group 1 (63.2% vs 42.0%, P<0.001). Multivariate analyses showed that N category, T category and chemotherapy were significant factors. The maximal dose (Dmax) to the temporal lobe was a significant factor affecting temporal lobe injury (TLI), with a hazard ratio of 1.26 (95% confidence interval (CI), 1.18–1.35; P<0.001) per 1-Gy increase. The 5-year TLI rate increased from 0.8% for 284 lobes with Dmax <65.77 Gy to 27.1% for 176 lobes with greater doses (P<0.001). Logistic regression showed that the hazard ratio attributed to the parotid gland mean dose was 1.36 (95% CI, 1.21–1.53; P<0.001) per 1-Gy increase. Chemotherapy was not a significant factor (P=0.211). With the application of IMRT, the incidence of radiation-related complications has been reduced except for TLI. The significant factors affecting the risk of TLI included T category, chemotherapy and Dmax.