Effects of neoadjuvant chemotherapy vs chemoradiotherapy in the treatment of esophageal adenocarcinoma: A systematic review and meta-analysis.

BACKGROUND: Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer; however, the superiority of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) is unclear. Therefore, a discussion of these two modalities is necessary. AIM: To investigate the benefits and complications of neoadjuvant modalities. METHODS: To address this concern, predefined criteria were established using the PICO protocol. Two independent authors performed comprehensive searches using predetermined keywords. Statistical analyses were performed to identify significant differences between groups. Potential publication bias was visualized using funnel plots. The quality of the data was evaluated using the Risk of Bias Tool 2 (RoB2) and the GRADE approach. RESULTS: Ten articles, including 1928 patients, were included for the analysis. Significant difference was detected in pathological complete response (pCR) [P < 0.001; odds ratio (OR): 0.27; 95%CI: 0.16-0.46], 30-d mortality (P = 0.015; OR: 0.4; 95%CI: 0.22-0.71) favoring the nCRT, and renal failure (P = 0.039; OR: 1.04; 95%CI: 0.66-1.64) favoring the nCT. No significant differences were observed in terms of survival, local or distal recurrence, or other clinical or surgical complications. The result of RoB2 was moderate, and that of the GRADE approach was low or very low in almost all cases. CONCLUSION: Although nCRT may have a higher pCR rate, it does not translate to greater long-term survival. Moreover, nCRT is associated with higher 30-d mortality, although the specific cause for postoperative complications could not be identified. In the case of nCT, toxic side effects are suspected, which can reduce the quality of life. Given the quality of available studies, further randomized trials are required.

Rational and design of prophylactic cranial irradiation (PCI) and brain MRI surveillance versus brain MRI surveillance alone in patients with limited-stage small cell lung cancer achieving complete remission (CR) of tumor after chemoradiotherapy: a multicenter prospective randomized study.

BACKGROUND: Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. METHODS: A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4-6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria. DISCUSSION: Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI.

Effects of bone marrow sparing radiotherapy on acute hematologic toxicity for patients with locoregionally advanced cervical cancer: a prospective phase II randomized controlled study.

OBJECTIVE: To evaluate effects of bone marrow sparing (BMS) radiotherapy on decreasing the incidence of acute hematologic toxicity (HT) for locoregionally advanced cervical cancer (LACC) patients treated by pelvic irradiation. MATERIALS AND METHODS: LACC patients were recruited prospectively from May 2021 to May 2022 at a single center and were evenly randomized into the BMS group and the control group. All patients received pelvic irradiation with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy and BM V40 < 25% in the BMS group was additionally prescribed. Acute HT was assessed weekly. Binary logistic regression model and receiver operating characteristic (ROC) curve were used for predictive value analysis. The trial was registered with Chinese clinical trial registry (ChiCTR2200066485). RESULTS: A total of 242 patients were included in the analysis. Baseline demographic, disease and treatment characteristics were balanced between the two groups. In the intention-to-treat population, BMS was associated with a lower incidence of grade ≥ 2 and grade ≥ 3 acute HT, leukopenia and neutropenia s(72.70% v 90.90%, P < 0.001*; 16.50% vs. 65.30%, P < 0.001*; 66.10% vs. 85.10%, P = 0.001*; 13.20% vs. 54.50%, P < 0.001*; 37.20% vs. 66.10%, P < 0.001*; 10.70% vs. 43.80%, P < 0.001*). BMS also resulted in decreased dose delivered to the organs at risk (OARs) including rectum, bladder and left and right femoral head. Univariate and multivariate analyses showed that BM V40 was an independent risk factor for grade ≥ 3 acute HT (odds ratio [OR] = 2.734, 95% confidence interval [CI] = 1.959-3.815, P < 0.001*). Cutoff value was 25.036% and area under the curve (AUC) was 0.786. The nomogram was constructed, which was rigorously evaluated and internally cross-validated, showing good predictive performance. CONCLUSIONS: Receiving BMS pelvic irradiation could reduce the incidence of acute HT in LACC patients, and BM V40 < 25% may be a significant factor in reducing the risks of acute HT.

The safety and efficacy of Compound Kushen Injection with chemoradiotherapy for the outcomes of lung and gastrointestinal cancers: A PRIMSA-compliant meta-analysis.

BACKGROUND: Compound Kushen injection (CKI) is a mixture of natural compounds extracted from Radix Sophorae and Smilax glabra Roxb. CKI, as an antitumor preparation, plays a vital role in the clinical treatment of lung and gastrointestinal cancers. METHODS: Electronic databases such as the China National Knowledge Infrastructure, Wanfang data, PubMed, EMBASE, and Web of Science were searched for studies. The included studies were evaluated according to the Cochrane Handbook for Systematic Reviews, and meta-analyses were performed using RevMan 5.3 software. RESULTS: Twenty-four randomized controlled trials were selected for meta-analysis. The outcomes showed that CKI adjuvant therapy significantly improved complete remission (CR) and partial response (PR) compared to patients without CKI treatment in gastrointestinal cancers (CR: odds ratio [OR] = 1.76, 95% confidence interval [CI]: [1.29, 2.41], P = .0004; PR: OR = 1.64, 95% CI: [1.29, 2.07], P =.0001), and lung cancer (CR: OR = 2.18, 95% CI: [1.36, 3.51], P = .001); PR: OR = 1.81, 95% CI: [1.31, 2.50], P = .0003). CKI adjuvant therapy had a statistically significant advantage in optimizing life and health status (quality of life [QOL] for gastrointestinal cancers: MD = 1.76, 95% CI: [6.41, 13.80], P = .001, and Karnofsky performance status [KPS] for gastrointestinal cancers: MD = 4.64, 95% CI: [2.72, 6.57], P = .001; KPS for lung cancer: MD = 6.24, 95% CI [1.78, 10.71], P = .006). CKI reduced the pain in lung cancer patients (MD = -1.76, 95% CI: [-1.94, -1.58], P < .00001), increased immunity level (MD = 2.51, 95% CI: [2.17, 2.85], P < .00001), and alleviated the adverse reactions for lung and gastrointestinal cancers (MD = 0.38, 95% CI: (0.32, 0.46); P < .00001). CONCLUSION: The combination of CKI and chemoradiotherapy for treating lung and gastrointestinal cancer has positive effects on short-term and long-term outcomes and has advantages over chemoradiotherapy alone regarding safety and efficacy.

Postoperative chemoradiotherapy in patients with locally advanced gastric cancer with poor pathologic response to neoadjuvant chemotherapy.

PURPOSE: To evaluate the effect of postoperative chemoradiotherapy (CRT) in patients with locally advanced gastric cancer (LAGC) who respond poorly to neoadjuvant chemotherapy (ChT). MATERIALS AND METHODS: The database of a tertiary medical center (2009-2020) was retrospectively reviewed for patients with LAGC in whom the initial treatment strategy consisted of perioperative ChT and surgery. Those who were subsequently referred for postoperative CRT because of a poor pathologic primary-tumor response (ypT3-4, ypN2-3, R1 resection) were selected for the study. CRT consisted of 45 Gy in 25 fractions of 1.8 Gy combined with capecitabine 825 mg/m2 twice daily on radiotherapy days or continuous infusion of 5-fluorouracil 180 mg/m2/day. RESULTS: The cohort included 26 patients of median age 61 years with LAGC (clinical stage IIA-III) after surgery with D1-D2 lymphadenectomy. R0 resection was achieved in 15 (58%). The pathological stage was III in 69% (IIA-IVA). Treatment was well tolerated. During a median follow-up time of 39 months, recurrences were documented in 14 patients (54%): 11 distant and 3 locoregional. Median progression-free survival was 23 months, and median overall survival was 65 months. Estimated 5-year survival rates were 42 and 54%, respectively. CONCLUSIONS: This small retrospective study suggests that in patients with LAGC who show a poor pathologic response to neoadjuvant ChT, a good outcome relative to reference arms in randomized trials can still be achieved with the addition of postoperative CRT. Further studies of the benefit of a tailored adaptive treatment approach to LAGC based on the response to neoadjuvant ChT are warranted.

Non-operative management in low-lying rectal cancers undergoing chemoradiation.

PURPOSE: To evaluate the outcomes of post-neoadjuvant chemoradiation (NACTRT) wait-and-watch Strategy (WWS) in distal rectal cancers. MATERIALS AND METHODS: All consecutive patients from December 2012 to 2019 diagnosed with distal rectal tumors (T2-T4 N0-N+) having a complete or near-complete response (cCR or nCR, respectively) post-NACTRT and wishing for the non-surgical treatment option of WWS were included in this study. Patients were observed with 3 monthly magnetic resonance imaging (MRIs), sigmoidoscopies, and digital rectal examination for 2 years and 6 monthly thereafter. Organ preservation rate (OPR), local regrowth rate (LRR), non-regrowth recurrence-free survival (NR-RFS) and overall survival (OAS) were estimated using the Kaplan-Meier method, and factors associated with LRR were identified on univariate and multivariate analysis using the log-rank test (P < 0.05 significant). RESULTS: Sixty-one consecutive patients post-NACTRT achieving cCR[44 (72%)] and nCR[17 (28%)], respectively, were identified. All patients received pelvic radiotherapy at a dose of 45-50Gy conventional fractionation and concurrent capecitabine. An additional boost dose with either an external beam or brachytherapy was given to 39 patients. At a median follow-up of 39 months, 11 (18%) patients had local regrowth, of which seven were salvaged with surgery and the rest are alive with the disease, as they refused surgery. The overall OPR, NR-RFS, and OS were 83%, 95%, and 98%, respectively. Seven (11%) patients developed distant metastasis, of which six underwent metastatectomy and are alive and well. LRR was higher in patients with nCR versus cCR (P = 0.05). CONCLUSION: The WWS is a safe non-operative alternative management for selected patients attaining cCR/nCR after NACTRT with excellent outcomes.

Immune checkpoint inhibitors combined with concurrent chemoradiotherapy in locally advanced esophageal squamous cell carcinoma.

Purpose: This study aims to evaluate the efficacy of immune checkpoint inhibitors (ICIs) combined with concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with locally advanced esophageal squamous cell carcinoma. Materials and methods: This retrospective cohort study included patients diagnosed with locally advanced esophageal squamous cell carcinoma who received either CCRT alone or CCRT combined with ICIs from April 2019 to February 2023. The primary endpoint was progression-free survival (PFS), and the secondary endpoint was overall survival (OS). Results: A total of 101 patients were enrolled, with 58 undergoing CCRT alone and 43 receiving CCRT+ICI. The CCRT+ICI group demonstrated a higher complete response rate compared to the CCRT alone group (11.6% vs. 1.7%, P = 0.037). However, no significant difference was observed in 1-year PFS (58.9% vs. 55.2%; hazard ratio [HR] = 1.26, 95% confidence interval [CI]: 0.70-2.26; P = 0.445) or 1-year OS (70.8% vs. 75.9%; HR = 1.21, 95% CI: 0.58-2.53; P = 0.613) between CCRT+ICI and CCRT alone groups. The CCRT alone group experienced a higher incidence of leukopenia of any grade (93.1% vs. 76.7%, P = 0.039) but a lower incidence of pneumonitis of any grade (36.2% vs. 65.1%, P = 0.008). Conclusion: CCRT+ICI may not lead to improved survival outcomes compared to CCRT alone in patients with locally advanced esophageal squamous cell carcinoma. These findings indicate the need for further investigation into this treatment approach.

Results of Definitive (Chemo)radiotherapy Using Computed Tomography-based Brachytherapy for Cervical Cancer.

BACKGROUND/AIM: Concurrent cisplatin-based chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer. Especially, CCRT with magnetic resonance imaging (MRI) or computed tomography-based image-guided brachytherapy (CT-based 3D-IGBT) for cervical cancer has resulted in good LC rates. However, progression-free survival (PFS) and overall survival (OS) rates for locally advanced cervical cancer are still low and could be improved. The aim of the study was to evaluate treatment efficacy and late toxicity of external beam radiotherapy (EBRT) and CT-based IGBT with or without concurrent chemotherapy in patients with squamous cell carcinoma of the uterine cervix and investigate patterns of failure. PATIENTS AND METHODS: We retrospectively analyzed clinical data of cervical squamous cell carcinoma patients treated with definitive radiotherapy with or without concurrent chemotherapy at Saitama Medical University International Medical Center. Local control (LC), PFS, patterns of failure, and late toxicity were the evaluated outcomes. RESULTS: Overall, 290 patients were enrolled in the study. Median follow-up was 51.5 months. During follow-up, 74 patients developed recurrence: 10 patients with intra-pelvic failure only, 45 with extra-pelvic failure only, and 19 with both. The 3-year LC was 100% for T1b-T2a, 96.8% for T2b, 89.5% for T3b, and 88.5% for T4 disease. The 3-year PFS was 100% for stage IB-IIA, 89.0% for stage IIB, 70.7% for stage IIIB, 72.6% for stage IIIC1r, and 40.1% for stage IVA. The incidence of grade 3-4 gastrointestinal and genitourinary toxicities was 3.0% and 1.7%, respectively. CONCLUSION: Combination of EBRT and CT-based IGBT with or without concurrent chemotherapy produced favorable LC with acceptable rates of late toxicities. However, extra-pelvic failures frequently occurred and PFS was less satisfactory in patients with stage III-IVA disease, which indicated the need for additional treatment in these patients.

Deletion of concurrent chemotherapy on the basis of sequential chemoradiotherapy for non-metastatic stage T4 nasopharyngeal carcinoma in IMRT era.

PURPOSE: Intensity-modulated radiotherapy (IMRT) combined with concurrent chemotherapy is deemed as the mainstay treatment in locoregionally advanced nasopharyngeal carcinoma (NPC). Nevertheless, the tolerance of severe acute toxicity of concurrent chemotherapy was unsatisfied. In addition, T4 is the predicting factor of poor prognosis for NPC patients. In this retrospective analysis, the long-term outcomes IMRT combined by induction chemotherapy deleting concurrent chemotherapy with or without adjuvant chemotherapy for T4 non-metastatic NPC were analyzed. MATERIALS AND METHODS: From January 2005 to November 2016, a total of 145 biopsy-proven non-metastatic T4 NPC was treated with IMRT combined by induction chemotherapy with or without adjuvant chemotherapy. The survival and side effects of the patients were analyzed. RESULTS: Median follow-up time was 74 months (ranges, 8-186 months). 10.0%, 61.3%, 27.3%, and 1.3% developed grade 1, 2, 3, and 4 mucositis during IMRT, respectively. 5.5% and 2.0% patients experienced grade 1 and 2 nausea and vomiting; no patients developed grade 3 or 4 nausea and vomiting. Of 145 patients enrolled, 5-year and 10-year overall survival(OS) rates were 73.7% and 53.9%, local progression-free survival(LPFS) rates were 86.1% and 71.6%, regional progression-free survival(RPFS) rates were 96.7% and 92.8%, distant metastasis-free survival (DMFS) rates were 86.7%, 78.2%, respectively. At the last follow-up, five patients developed cranial nerve injury, one patient developed mandibular bone necrosis, four patients developed temporal lobe injury, four patients developed nasopharyngeal massive hemorrhage (three cases after recurrence and one case without recurrence), and five patients developed second primary tumor. CONCLUSION: The survival outcomes of treating T4 NPC IMRT combined by induction chemotherapy deleting concurrent chemotherapy with or without adjuvant chemotherapy are encouraging. Moreover, mucosal reaction, nausea, and vomiting reaction were reduced during IMRT.

Durvalumab in combination with chemoradiotherapy in patients with head and neck squamous cell carcinoma: Results from the Phase 1 CLOVER study.

BACKGROUND: The Phase 1 CLOVER study (NCT03509012) assessed durvalumab in combination with concurrent chemoradiotherapy (cCRT) in patients with advanced solid tumors; we report results from the head and neck squamous cell carcinoma (HNSCC) cohort. METHODS: Patients with histologically/cytologically confirmed locally advanced HNSCC, eligible for definitive cCRT and not considered for primary surgery, received durvalumab plus cisplatin and concurrent external beam radiation. Objectives were to assess safety/tolerability and preliminary efficacy. RESULTS: Eight patients were enrolled. The most frequent any-cause adverse events (AEs) were nausea and radiation skin injury (each n = 5); most frequent grade 3/4 AEs were lymphopenia and stomatitis (each n = 3). No patients had dose-limiting toxicities. Objective response rate was 71.4% (5/7 patients; four complete responses, one partial response); disease control rate was 85.7% at 18 weeks and 83.3% at 48 weeks. CONCLUSIONS: Durvalumab plus cCRT was tolerable and active in patients with unresected, locally advanced HNSCC.

Endostar acts as a pneumonitis protectant in patients with locally advanced non-small cell lung cancer receiving concurrent chemoradiotherapy.

BACKGROUND: CCRT is presently the standard treatment for LA-NSCLC. RP is one of the main obstacles to the completion of thoracic radiation therapy, resulting in limited survival benefits in NSCLC patients. This research aims to explore the role of Endostar in the occurrence of grade≥2 RP and clinical curative effect in LA-NSCLC patients. METHODS: This study retrospectively analyzed 122 patients with stage III NSCLC who received CCRT from December 2008 to December 2017, or Endostar intravenous drip concurrently with chemoradiotherapy (Endostar + CCRT group). Standard toxicity of the pneumonitis endpoint was also collected by CTCAE V5.0. We further summarized other available studies on the role of Endostar in the prognosis of NSCLC patients and the incidence of RP. RESULTS: There were 76 cases in the CCRT group and 46 cases in the CCRT+ Endostar group. In the CCRT+ Endostar group, the occurrence of grade ≥2 RP in patients with V20Gy ≥25% was significantly higher than that in patients with V20Gy < 25% (p = 0.001). In the cohorts with V20Gy < 25%, 0 cases of 29 patients treated with Endostar developed grade ≥2 RP was lower than in the CCRT group (p = 0.026). The re-analysis of data from other available studies indicated that Endostar plus CCRT could be more efficient and safely in the occurrence of grade≥2 RP with LA-NSCLC. CONCLUSIONS: When receiving CCRT for LA-NSCLC patients, simultaneous combination of Endostar is recommended to enhance clinical benefit and reduce pulmonary toxicity.

Risk stratification of LA-NPC during chemoradiotherapy based on clinical classification and TVRR.

PURPOSE: To investigate the correlation between tumor volume reduction rate (TVRR) and prognosis in patients with diverse clinical types of nasopharyngeal carcinoma (NPC) undergoing chemoradiotherapy, thereby aptly categorizing risks and directing the personalized treatment of NPC. MATERIALS AND METHODS: A total of 605 NPC patients with varying clinical types were enrolled in this study and subsequently segregated into six subgroups based on their clinical types and TVRR. To accentuate the efficacy of grouping, Groups 1-6 underwent clustered analysis of hazard atio (HR) values pertaining to progression-free survival (PFS), forming three risk clusters denoted as low, intermediate, and high. The log-rank test was employed to discern differences, and R 4.1.1 was utilized for cluster analysis. RESULTS: According to survival rates, we classified the first (G2 and G4), second (G1 and G6), and third (G3 and G5) risk clusters as low-, intermediate-, and high-risk, respectively. When comparing risk stratification with the 8th edition of the TNM staging system, our classification exhibited superior predictive prognostic performance. Subgroup analysis of treatments for each risk cluster revealed that the PFS in the neoadjuvant chemotherapy (NACT) + concurrent chemoradiotherapy (CCRT) group surpassed that of the CCRT group significantly (p < 0.05). CONCLUSION: The reliance on clinical types and TVRR facilitates risk stratification of NPC during chemoradiotherapy, providing a foundation for physicians to tailor therapeutic strategies. Moreover, the risk cluster delineated for NPC patients during the mid-term of chemoradiotherapy stands as an independent prognostic factor for progression-free survival (PFS), overall survival (OS), distantmetastasis-free survival (DMFS), and local recurrence-free (LRRFS) posttreatment. Additionally, individuals in the high-risk cluster are recommended to undergo adjuvant chemotherapy after CCRT.

Efficacy and Safety of Preoperative Transcatheter Rectal Arterial Chemoembolisation in Patients with Locally Advanced Rectal Cancer: Results from a Prospective, Phase II PCAR Trial.

AIMS: The PCAR study aimed to assess the efficacy and safety of preoperative transcatheter rectal arterial chemoembolisation (TRACE) in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: This was a single-centre, prospective, phase II trial conducted in China. Eligible patients were adults aged 18 years and older with histologically confirmed stage II or III rectal carcinoma and an Eastern Cooperative Oncology Group performance status of 0-1. Patients received TRACE with oxaliplatin, followed by radiotherapy with a cumulative dose of 45 Gy (1.8 Gy/time/day, five times a week for 5 weeks) and received oral S1 capsules twice daily (7 days a week for 4 weeks). Patients underwent total mesorectal excision 4-8 weeks after the completion of chemoradiotherapy, followed by mFOLFOX6 or CAPOX regimens for 4-6 months. The hypothesis of this study was that adding TRACE to preoperative neoadjuvant chemoradiotherapy would improve tumour regression and prognosis. The primary end point was the pathological complete response rate; secondary end points included the major pathological response rate, anal preservation rate, 5-year disease-free survival (DFS), 5-year overall survival and treatment-related adverse events. RESULTS: In total, 111 LARC patients received TRACE and subsequent scheduled treatment plans. The pathological complete response and major pathological response rates were 20.72% and 48.65%, respectively. The 5-year DFS and 5-year overall survival were 61.89% (95% confidence interval 51.45-74.45) and 74.80% (95% confidence interval 65.05-86.01), respectively. Grade 3-4 toxicities were reported in 29 patients (26.13%). The postoperative complication rate was 21.62%, without serious surgical complications. Multivariate Cox regression analysis showed that ypN stage (hazard ratio = 4.242, 95% confidence interval 2.101-8.564, P = 0.00017) and perineural invasion (hazard ratio = 2.319, 95% confidence interval 1.058-5.084, P = 0.0487) were independent risk factors associated with DFS, whereas ypN stage (hazard ratio = 3.164, 95% confidence interval 1.347-7.432, P = 0.0101), perineural invasion (hazard ratio = 4.118, 95% confidence interval 1.664-10.188, P = 0.0134) and serum carbohydrate antigen 199 (CA199; hazard ratio = 4.142, 95% confidence interval 1.290-13.306, P = 0.0344) were independent predictors for overall survival. CONCLUSION: The current study provides evidence that adding TRACE to neoadjuvant chemoradiotherapy can improve the pathological remission rate in LARC patients with acceptable toxicity. Given its promising effectiveness and safe profile, incorporating TRACE into the standard treatment strategy for patients with LARC should be considered.

Impact of fosaprepitant in the prevention of nausea and emesis in head and neck cancer patients undergoing cisplatin-based chemoradiation: a pilot prospective study and a review of literature.

PURPOSE: Cisplatin-based chemoradiotherapy (CRT) is standard treatment for head and neck squamous cell carcinoma (HNSCC). However, IMRT may increase chemotherapy-induced nausea and vomiting (CINV). The purpose of this study is to investigate the effect of fosaprepitant in preventing CINV. METHODS: An infusion of 150 mg fosaprepitant was given through a 30 min. We assessed acute toxicity using CTCAE v.4 and the incidence of CINV using the FLIE questionnaire. The evaluation of CINV was done at the second and fifth weeks of CRT and 1 week after the end. The EORTC QLQ-HN 43 questionnaire was administered before treatment beginning (baseline), at second (T1) and fifth (T2) weeks. A dosimetric analysis was performed on dorsal nucleus of vagus (DVC) and area postrema (AP). RESULTS: Between March and November 2020, 24 patients were enrolled. No correlation was found between nausea and DVC mean dose (p = 0.573), and AP mean dose (p = 0.869). Based on the FLIE questionnaire, patients reported a mean score of 30.5 for nausea and 30 for vomiting during week 2 and 29.8 for nausea and 29.2 for vomiting during week 5. After treatment ended, the mean scores were 27.4 for nausea and 27.7 for vomiting. All patients completed the EORTC QLQ-HN 43. Significantly higher scores at T2 assessment than baseline were observed. CONCLUSIONS: The use of fosaprepitant in preventing CINV reduced incidence of moderate to severe nausea and vomiting. No correlation has been found between nausea and median dose to DVC and AP.

Camrelizumab and apatinib plus induction chemotherapy and concurrent chemoradiotherapy in stage N3 nasopharyngeal carcinoma: a phase 2 clinical trial.

The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Patients with N3 nasopharyngeal carcinoma have a high risk of distant metastasis, however, if the addition of immunotherapy to standard treatment could improve efficacy is unclear. In this phase II clinical trial (ChiCTR2000032317), 49 patients with stage TanyN3M0 nasopharyngeal carcinoma were enrolled and received the combination of three cycles of induction chemotherapy, camrelizumab and apatinib followed by chemoradiotherapy. Here we report on the primary outcome of distant metastasis-free survival and secondary end points of objective response rate, failure-free survival, locoregional recurrence-free survival, overall survival and toxicity profile. After induction therapy, all patients had objective response, including 13 patients (26.5%) with complete response. After a median follow-up of 28.7 months, the primary endpoint of 1-year distant metastasis-free survival was met for the cohort (1-year DMFS rate: 98%). Grade≥3 toxicity appeared in 32 (65.3%) patients, with the most common being mucositis (14[28.6%]) and nausea/vomiting (9[18.4%]). In this work, camrelizumab and apatinib in combination with induction chemotherapy show promising distant metastasis control with acceptable safety profile in patients with stage TanyN3M0 nasopharyngeal carcinoma.

A bioconvergence study on platinum-free concurrent chemoradiotherapy for the treatment of HPV-negative head and neck carcinoma.

Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is characterized by high rate of recurrence, resulting in a poor survival. Standard treatments are associated with significant toxicities that impact the patient's quality of life, highlighting the urgent need for novel therapies to improve patient outcomes. On this regard, noble metal nanoparticles (NPs) are emerging as promising agents as both drug carriers and radiosensitizers. On the other hand, co-treatments based on NPs are still at the preclinical stage because of the associated metal-persistence.In this bioconvergence study, we introduce a novel strategy to exploit tumour chorioallantoic membrane models (CAMs) in radio-investigations within clinical equipment and evaluate the performance of non-persistent nanoarchitectures (NAs) in combination with radiotherapy with respect to the standard concurrent chemoradiotherapy for the treatment of HPV-negative HNSCCs. A comparable effect has been observed between the tested approaches, suggesting NAs as a potential platinum-free agent in concurrent chemoradiotherapy for HNSCCs. On a broader basis, our bioconvergence approach provides an advance for the translation of Pt-free radiosensitizer to the clinical practice, positively shifting the therapeutic vs. side effects equilibrium for the management of HNSCCs.

Predictive value of delta radiomics in xerostomia after chemoradiotherapy in patients with stage III-IV nasopharyngeal carcinoma.

BACKGROUND: Xerostomia is one of the most common side effects in nasopharyngeal carcinoma (NPC) patients after chemoradiotherapy. To establish a Delta radiomics model for predicting xerostomia secondary to chemoradiotherapy for NPC based on magnetic resonance T1-weighted imaging (T1WI) sequence and evaluate its diagnostic efficacy. METHODS: Clinical data and Magnetic resonance imaging (MRI) data before treatment and after induction chemotherapy (IC) of 255 NPC patients with stage III-IV were collected retrospectively. Within one week after CCRT, the patients were divided into mild (92 cases) and severe (163 cases) according to the grade of xerostomia. Parotid glands in T1WI sequence images before and after IC were delineated as regions of interest for radiomics feature extraction, and Delta radiomics feature values were calculated. Univariate logistic analysis, correlation, and Gradient Boosting Decision Tree (GBDT) methods were applied to reduce the dimension, select the best radiomics features, and establish pretreatment, post-IC, and Delta radiomics xerostomia grading predictive models. The receiver operating characteristic (ROC) curve and decision curve were drawn to evaluate the predictive efficacy of different models. RESULTS: Finally, 15, 10, and 12 optimal features were selected from pretreatment, post-IC, and Delta radiomics features, respectively, and a xerostomia prediction model was constructed with AUC values of 0.738, 0.751, and 0.843 in the training set, respectively. Only age was statistically significant in the clinical data of both groups (P < 0.05). CONCLUSION: Delta radiomics can predict the degree of xerostomia after chemoradiotherapy for NPC patients and it has certain guiding significance for clinical early intervention measures.

Retrospective Analysis of Definitive Chemoradiotherapy With FOLFOX in Patients With Esophageal Cancer Intolerant to Cisplatin.

BACKGROUND/AIM: Definitive chemoradiotherapy with cisplatin (CDDP) plus 5-fluorouracil is the standard treatment for locally advanced esophageal squamous cell carcinoma (LA-ESCC); however, CDDP is unsuitable for patients with cardiac and/or renal dysfunction. Based on the results of the PRODIGE5/ACCORD17 trial, 5-fluorouracil and leucovorin with oxaliplatin plus radiotherapy (FOLFOX-RT) has been recognized as a treatment option. However, the efficacy and safety of FOLFOX-RT is still unclear in Japan. PATIENTS AND METHODS: Medical records were reviewed for patients with LA-ESCC who received FOLFOX-RT between April 2019 and July 2021 at our institution. We evaluated complete response rate, progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: Fifteen patients were analyzed and median age was 72.5 years (range=51-83 years). All patients completed three courses of FOLFOX and the planned radiotherapy. The complete response rate was 40.0%. With a median follow-up of 10.6 months, the 6-month PFS rate was 63.0% (95%CI=32.3-82.8%), and the 6-month OS rate was 85.7% (95%CI=53.9-96.2%). Common adverse events were esophagitis (80.0%), leukopenia (53.3%), fatigue (53.3%), and neutropenia (46.7%). Only one patient had grade 4 esophageal perforation. CONCLUSION: FOLFOX-RT for LA-ESCC was well tolerated and could be a treatment option for CDDP-intolerant patients.

Comparison of Efficacy and Safety of First-Line Treatment Options for Unresectable Stage III Non-Small Cell Lung Cancer: A Retrospective Analysis.

Background: Based on PACIFIC trial, durvalumab as consolidation therapy following concurrent chemoradiotherapy (cCRT) has been a new standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). In clinical applications, there are heterogeneous adjustments or novel strategies following specialized discussions in experienced multidisciplinary teams. This study retrospectively compared the efficacy and safety of different first-line treatments for unresectable stage III NSCLC. Methods: We retrospectively analyzed 397 patients who received first-line treatment for unresectable stage III NSCLC. Comparisons and statistical analyses of treatment were made in terms of efficacy and safety. Adverse events and responses were assessed using CTCAE v5.0 and RECIST v1.1. The progression-free survival (PFS) was estimated using the Kaplan-Meier method or the Cox survival regression model and compared using the log-rank test. Results: In wild-type driver genes group, the objective response rate (ORR), disease control rate (DCR), and median PFS (mPFS) were prolonged in the radiotherapy group compared to those in the nonradiotherapy group (ORR: 50.94% vs. 30.06%, p < 0.001; DCR: 98.11% vs. 80.37%, p < 0.001; and mPFS: 21.00 vs. 8.20 months, p < 0.001). The incidence of pneumonia at any grade in the radiotherapy group was higher than that in the nonradiotherapy group (9.43% vs. 2.45%, p = 0.008). In the radiotherapy group, the chemoradiotherapy (CRT) plus immunotherapy subgroup had longer mPFS than the CRT subgroup, with increased toxicity at any grade (24.60 vs. 17.90 months, p = 0.025, and 83.17% vs. 65.52%, p = 0.011). In the nonradiotherapy group, the DCR and mPFS were higher in the chemotherapy plus immunotherapy subgroup than in the chemotherapy subgroup, with increased toxicity at any grade (DCR: 93.67% vs. 67.86%, p < 0.001; mPFS: 13.53 vs. 5.07 months, p < 0.001; and 68.35% vs. 41.67%, p = 0.001). In the mutant driver genes group, the efficacy did not significantly differ among the radiotherapy subgroup, targeted therapy subgroup, and radiotherapy plus targeted therapy subgroup (ORR: p = 0.633; mPFS: p = 0.450). Conclusions: For unresectable stage III NSCLC patients with wild-type driver genes, the combination of radiotherapy and immunotherapy in the initial treatment was essential to significantly improve the efficacy. For patients with mutant driver genes, radiotherapy, targeted therapy, and the combination of radiotherapy and targeted therapy showed similar short-term efficacy.

Treatment for locally resectable stage IIIC1r cervical cancer: surgery or chemoradiotherapy?

OBJECTIVE: The aim of this study was to compare the therapeutic value and treatment-related complications of radical hysterectomy with those of concurrent chemoradiotherapy (CCRT) for locally resectable (T1a2-T2a1) stage IIIC1r cervical cancer. METHODS: A total of 213 patients with locally resectable stage IIIC1r cervical cancer who had been treated at Jiangxi Maternal and Child Health Care Hospital between January 2013 and December 2021 were included in the study and classified into two groups: surgery (148 patients) and CCRT (65 patients). The disease-free survival (DFS) rate, overall survival (OS) rate, side effects, and economic costs associated with the two groups were compared. RESULTS: 43.9% (65/148) patients in the surgical group had no pelvic lymph node metastasis, and 21of them did not require supplementary treatment after surgery due to a low risk of postoperative pathology. The median follow-up time was 46 months (range: 7-108 months). The five-year DFS and OS rates of the surgery group were slightly higher than those of the CCRT group (80.7% vs. 75.1% and 81.6% vs. 80.6%, respectively; p > 0.05). The incidences of grade III-IV gastrointestinal reactions in the surgery and CCRT groups were 5.5% and 9.2%, respectively (p = 0.332). Grade III-IV myelosuppression was identified in 27.6% of the surgery group and 26.2% of the CCRT group (p = 0.836). The per capita treatment cost was higher for the surgery group than for the CCRT group (RMB 123, 918.6 0 vs. RMB 101, 880.90, p = 0.001). CONCLUSION: The therapeutic effects and treatment-related complications of hysterectomy and CCRT are equivalent in patients with locally resectable stage IIIC1r cervical cancer, but surgery can provide accurate lymph node information and benefit patients with unnecessary radiation.