Concurrent Intensity-modulated Radiotherapy Research Articles

Capecitabine or Capecitabine Plus Oxaliplatin Versus Fluorouracil Plus Cisplatin in Definitive Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (CRTCOESC): A Multicenter, Randomized, Open-Label, Phase 3 Trial.

This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC). Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs). A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403). Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.

Treatment Outcomes of Concurrent Nimotuzumab with Intensity Modulated Radiotherapy in Advanced Nasopharyngeal Carcinoma Patients Unfit for Concurrent Chemoradiotherapy: A Single Institute Experience

To assess the safety and efficacy of intensity-modulated radiotherapy (IMRT) combined with nimotuzumab for patients with locally advanced nasopharyngeal carcinoma (LA-NPC) medically unfit to receive concomitant chemotherapy. From 2016.6 to 2020.9, 34 newly diagnosed patients with local-regional advanced NPC medically unfit for concurrent chemoradiation had undergone definitive radiotherapy and were retrospectively evaluated. All patients were treated with IMRT combined treatment modality of nimotuzumab with or without cisplatin-based induction chemotherapy. Nimotuzumab was administered concurrently with IMRT at a weekly dose of 200 mg. Acute and late radiation-related toxicities were evaluated based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 during and after IMRT. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate prognostic analyses were performed by using the Cox proportional hazard model. The median follow-up time for the entire group was 15 months (range 5 to 55 months). At the time of this analysis, a total of 2 cases developed loco-regional recurrence. In addition, 4 patients developed distant metastasis. There was a total of 5 deaths: 3 patients died from distant metastasis, 1 patient died from the progression of loco-regional disease after recurrence, and the causes of death for the additional 1 case was a nasopharyngeal ulcer and deadly bleeding. The 1-year OS rate of the whole cohort was 87.9%, and the 1-year LFFR, DFFR, and PFS rates were 100%, 91.0%, and 91.0%, respectively. During the period of concurrent nimotuzumab and IMRT, no grade 3-4 hematologic toxicities and dermatitis were observed. Grade 3-4 radiotherapy-related oral mucositis was reported in 7 patients (20.6%). No infusion reaction was observed. No acneiform eruptions were found among these patients. The most commonly observed late complication was xerostomia. The degree of dry mouth in most patients was mild-to-moderate at the time of the last follow-up. Finally, 7 patients developed either unilateral or bilateral hearing impairment. One female patient experienced a nasopharyngeal ulcer and deadly bleeding after 5 months of completion of radiotherapy. Concurrent nimotuzumab with IMRT for the treatment of LA-NPC was well tolerated, with encouraging survival data, and it could be an effective treatment alternative for patients with LA-NPC medically unfit for concomitant chemotherapy. Further clinical trials are needed to confirm these findings.

Capecitabine/cisplatin combined with concurrent intensity-modulated radiation therapy: a feasible therapeutic strategy for anal squamous cell carcinoma.

To evaluate the efficacy and safety of capecitabine/cisplatin (XP) combined with intensity-modulated radiation therapy (IMRT) in patients with non-metastatic anal squamous cell carcinoma (ASCC). All patients with ASCC who received radical concurrent chemoradiotherapy in the past 8years were screened. Patients who received XP or mitomycin/5-fluorouracil (MF) were selected and analyzed retrospectively. ASCC is an uncommon cancer, there were 36 patients were included in our study. The XP group and MF group included 18 patients each. The clinical complete response (cCR) rates in the XP group and the MF group were 94.4% and 88.9%, respectively (P = 1). The 2-year local control (LC), disease-free survival (DFS), and colostomy-free survival (CFS) rates were higher in the XP group than in the MF group (100% vs 93.3%, P = 0.32). Hematologic toxicities, especially grade ≥ 3 leukopenia (11.1% vs 44.4%, P = 0.06) and neutropenia (5.6% vs 61.1%, P = 0.001), were lower in the XP group than MF group. As a result of fewer side effects, fewer patients in the XP group demanded the dose reduction of chemotherapy (11.1% vs 50%, P = 0.03) and radiation interruption (55.6% vs 77.8%, P = 0.289). Delayed radiotherapy was shorter in the XP group (2.5 vs 6.5days, P = 0.042) than in the MF group. The XP regimen was as effective as the MF regimen in non-metastatic ASCC. Compared with the standard MF regimen, XP combined with IMRT showed higher treatment completion and lower toxicities. It could be considered a feasible alternative for patients with non-metastatic ASCC.

Concurrent intensity-modulated radiation therapy and chemotherapy plus nimotuzumab for locally advanced cervical squamous cell cancer: A long-term follow-up result

The study aimed to evaluate the safety and efficacy of concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy plus nimotuzumab for the treatment of locally advanced cervical squamous cell cancer (LACSCC). From December 2013 to March 2017, 34 patients with stages IB2–IVA (FIGO 2009) cervical squamous cell cancer were enrolled and received concurrent chemoradiotherapy plus nimotuzumab. The prescription radiation dose was 50.4 Gy/28 F on the pelvic field with or without extended-field radiation. An additional 30–36 Gy to Point A was delivered with high-dose-rate brachytherapy. Cisplatin 40 mg/m2 and nimotuzumab 200 mg were infused intravenously weekly. The main and secondary outcome measures were toxicity evaluated using common terminology criteria for adverse events 4.03. and the outcome evaluated using response evaluation criteria in solid tumors 1.1, respectively. The median follow-up duration was 66 months (13 – 98 months). All patients received 6 times of IMRT, brachytherapy, and nimotuzumab. Among them, 24 received six cycles of chemotherapy, while 11 received 4–5 cycles. No life-threatening toxicity was found. The incidence of acute Grade 3 bone marrow depression was 52.9% (18/34), and Grade 3 gastrointestinal tract reaction was 8.8% (3/34). The incidence of late toxicities was 58.8% (20/34), including vaginal-rectal fistula, intestinal obstruction, rectal hemorrhage, hematuria, vaginal stenosis, and paresthesia. About 90% of those were Grades 1–2. Complete response was achieved in 33 cases (97.1%). The 3-year disease-free survival, local progression-free survival (LPFS), and overall survival rates were 79.4%, 91.2%, and 82.4%, respectively. The corresponding 5-year values were 79.4%, 91.2%, and 79.3%. In conclusion, concurrent IMRT and chemotherapy plus nimotuzumab may represent a well-tolerated and effective treatment regimen in patients with LACSCC.

Individualized Concurrent Chemotherapy for Patients with Stage III-IVa Nasopharyngeal Carcinoma Receiving Neoadjuvant Chemotherapy Combined with Definitive Intensity-Modulated Radiotherapy.

This retrospective study aimed to re-evaluate the effect of concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT). A total of 498 patients who received neoadjuvant chemotherapy (NCT) combined with concurrent chemoradiotherapy (CCRT) or IMRT were retrospectively reviewed. The distribution of baseline characteristics was balanced using propensity score matching. Additionally, the results of NCT+IMRT and NCT+CCRT were compared using Kaplan-Meier survival analysis, and differences in survival rates were analyzed using the log rank test. There were no significant differences in overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and local progression-free survival (LRFS) between the two groups. Patients were further categorized into risk subgroups based on pretreatment Epstein-Barr virus (EBV) DNA cutoff values using receiver operating characteristic curve analysis. There were no statistically significant differences in OS, PFS, DMFS, and LRFS between patients who received NCT+CCRT and NCT+IMRT in the high-risk group. In the low-risk group, although there were no differences between NCT+CCRT and NCT+IMRT in OS, PFS, and LRFS, patients who received NCT+CCRT had better DMFS than those who received NCT+IMRT. Pretreatment EBV DNA level can be used to individualize concurrent chemotherapy for patients with locally advanced NPC. Patients with low pretreatment EBV DNA levels may benefit from concurrent chemotherapy, whereas those with high levels may not. Other treatment modalities need to be explored for high-risk patients to improve their prognosis.

Adding Concurrent Chemotherapy Significantly Improves the Survival of Stage II-IVb Nasopharyngeal Carcinoma Patients Treated With Concurrent Anti-EGFR Agents.

ObjectiveAnti-EGFR Targeted agents were found to be capable of modulating the antitumor immunity in head and neck cancer and become more and more frequently used in the treatment of nasopharyngeal carcinoma(NPC). We aimed to explore whether adding concurrent chemotherapy influences the survival outcome of patients with stage II-IVb NPC treated with concurrent anti-EGFR agents and intensity-modulated radiation therapy (IMRT) and explore other prognostic factors for the patients.Materials and MethodsA total of 656 stage II-IVb NPC patients treated with concurrent anti-EGFR agents plus IMRT between January 2011 and November 2015 were enrolled. Firstly, from these patients, a well-balanced cohort of 302 patients who received concurrent chemotherapy was created by matching potential prognostic factors. Furthermore, for all 656 stage II-IVb NPC patients, univariate and multivariate analyses of overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) were conducted to identify prognostic factors and to confirm the findings from the matching cohort.ResultsCompared with concurrent anti-EGFR agents alone, combining concurrent cisplatin and anti-EGFR agents significantly improved the OS (5-year 94.7% versus 84.3%, P=0.012) and PFS (5-year 82.0% versus 71.7%, P=0.039) of NPC patients with more severe hematologic toxicity and mucositis. The independent prognostic factors identified by multivariate analysis of OS and PFS included concurrent chemotherapy, epstein-barr virus(EBV) status and clinical stage. Patients treated without induction chemotherapy (IC) may achieve more benefits from the addition of concurrent chemotherapy to concurrent anti-EGFR agents.ConclusionsFor stage II-IVb NPC patients treated with concurrent anti-EGFR agents, the addition of concurrent chemotherapy can significantly improve the survival outcome.

Nasopharyngeal cancer in non-endemic areas: Impact of treatment intensity within a large retrospective multicentre cohort

AimRecommendations for managing patients with nasopharyngeal carcinoma (NPC) in non-endemic areas are largely derived from studies conducted in endemic areas. We analysed the impact of treatment approaches on survival in non-endemic areas. MethodsIn an international, multicentre, retrospective study, we analyse consecutive patients with NPC diagnosed between 2004 and 2017 in 36 hospitals from 11 countries. Treatment was categorised as non-intensive (NIT), including radiotherapy alone or concomitant chemoradiotherapy (cCRT), and intensive (IT) including cCRT preceded by and/or followed by chemotherapy (CT). The impact of IT on overall survival (OS) and disease-free survival (DFS) was adjusted for all the available potential confounders. ResultsOverall, 1021 and 1113 patients were eligible for overall survival (OS) and disease-free survival (DFS) analyses, respectively; 501 and 554 with Epstein Barr-encoded RNA (EBER) status available. In the whole group, 5-year OS was 84% and DFS 65%. The use of NIT was associated with a risk of death or recurrence 1.37 times higher than patients receiving IT. Patients submitted to NIT and induction CT + concurrent concomitant chemo and three-dimensional Conformal Radiation Therapy (3DCRT) had a risk of death or recurrence 1.5 and 1.7 times higher than patients treated with induction CT + cCRT with intensity-modulated radiotherapy (IMRT), respectively. The IT had no impact on OS in neither patients with EBER+ nor in patients with EBER-; IT showed better DFS in EBER+ but not in patients with EBER-. ConclusionsIn low-incidence areas, patients with NPC treated with induction CT followed by concurrent IMRT cCRT achieved the highest DFS rate. The benefit of IT on DFS was restricted to patients with EBER+, suggesting that additional therapy offers no advantages in EBER- cases.

Intensity Modulated Radiation Therapy and Concurrent Chemotherapy for Locally Advanced Cervical Cancer Not Amenable to Brachytherapy

<h3>Hypothesis</h3> Cervical cancer patients ineligible for brachytherapy due to tumor geometry suffer poor local control and survival outcomes despite treatment with concurrent IMRT and chemotherapy. <h3>Purpose/Objective(s)</h3> In this study of patients with cervical cancer tumors too large for brachytherapy boost, we report tumor control and toxicity outcomes of patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy. <h3>Materials/Methods</h3> We performed a retrospective study of patients with FIGO 2018 stage III-IVB cervical cancer treated with high dose IMRT and concurrent cisplatin without brachytherapy at a tertiary academic center from 2005 – 2020. All patients underwent FDG-PET/CT and were examined by an experienced gynecologic brachytherapist. Patients received 48.6-50.4 Gy in 25 to 35 fractions to the cervix, pelvis, and if involved on FDG-PET, paraaortic, and supraclavicular lymph nodes with IMRT. Lymph nodes greater than 3 cm received a simultaneous boost to a total dose of 60 Gy. The primary metabolically active cervical tumor received a simultaneous or sequential boost without additional planning margin to a total dose of 60-70.2 Gy with concurrent weekly cisplatin or carboplatin. Toxicity is reported with CTCAEv5. <h3>Results</h3> Twenty patients out of 1005 (2%) were identified with median age of 55 (range 37 – 76) years. Sixty percent were Caucasian, 35% black, 5% Asian. Median metabolic primary tumor volume was 111 cm3 (range 26 – 473). Nineteen (95%) had squamous histology and one (5%) had adenosquamous. Median follow up was 15 months (range 2 - 154). 7 (35%) patients had PET positive pelvic lymph nodes, 5 (25%) paraaortic, and 3 (15%) supraclavicular. Classic FIGO stage was: III 7 (35%), IVA 11 (55%), IVB 2 (10%). FIGO 2018 stage was: III 3 (15%), IVA 9 (45%), IVB 8 (40%). Five (20%) patients were disease free at the end of follow up (III 1 (33%), IVA 3 (33%), IVB 1 (13%)). One- and 2-year freedom from local progression were 70% and 60%, respectively. One and 2-year OS were 60% and 35%, respectively. Grade 3 anemia and nausea occurred in 4 (20%), and 2 (10%) patients, respectively. Grade 4 diarrhea and nausea occurred in 1 (5%) and 3 (15%) patients, respectively. Two (10%) patients died of treatment-related toxicity. <h3>Conclusion</h3> Our study shows that patients ineligible for brachytherapy suffer poor local control and survival outcomes. Grade 4-5 toxicity occurred in 25% of patients. Novel radiation techniques for this patient population should be further explored.

The effect of combined TPF and intensity modulated radiotherapy after TPF induction chemotherapy on locally advanced nasopharyngeal carcinoma: a retrospective analysis.

To evaluate the efficacy and toxicity of docetaxel, cisplatin, and fluorouracil (TPF) regimen followed by intensity modulated radiotherapy (IMRT) on locally advanced nasopharyngeal carcinoma (NPC). A total of 150 patients with locally advanced NPC [American Joint Committee on Cancer (AJCC) 2009 stage IIIa-IVb] received 2 or 3 cycles of a TPF regimen as induction chemotherapy. A group of 67 participants (TPF group) continued to receive TPF chemotherapy and radiotherapy, and the remaining 83 participants (P group) received cisplatin chemotherapy and radiotherapy. A median follow-up of 35 months (4-66 months) showed that there was no significant difference between P group and TPF group in progression-free survival (PFS) and overall survival (OS). The incidence rate of myelosuppression at 3-4 degrees was 16.9% and 34.3% in the P group and TPF group (P=0.029), respectively, and the oral mucosa reaction at 3-4 degrees was 18.1% and 37.3% in the P group and TPF group, respectively (P=0.007). The 3-4-degree skin reaction in the P group and TPF group was 15.7% and 29.9% (P=0.030), respectively. The rate of liver function injury in the P group was significantly lower than that in TPF group (P<0.05). Compared with concurrent cisplatin chemotherapy and radiotherapy, the concurrent TPF regimen and IMRT showed no significant improvement in OS and PFS in patients with advanced NPC, but exhibited more severe hematologic toxicity, oral mucosal responses, skin reactions, and liver functional impairment.

A Study Comparing Acute Toxicities of Cetuximab and Cisplatin in Patients Undergoing Definitive Chemoradiation With Intensity-Modulated Radiotherapy for Locally Advanced Carcinoma Head and Neck.

PurposeTo study the acute toxicities of weekly cetuximab used concurrently with intensity-modulated radiotherapy (IMRT) versus weekly cisplatin with concurrent IMRT in locoregionally advanced head and neck squamous cell carcinoma (HNSCC).Materials and methodsFifty eligible patients were randomly assigned to study group (cetuximab group) and control group (cisplatin group) to receive cetuximab 400 mg/m2 intravenously one week prior to the start of RT followed by 250 mg/m2/week, or weekly cisplatin intravenously 40 mg/m2, during RT. RT dose received was 70Gy in 35 fractions with 2Gy/fraction in both the arms with IMRT technique. Patients are reviewed every week and Patients were evaluated for acute toxicities according to radiation therapy oncology group (RTOG) toxicity scoring criteria and toxicities grade was reported.ResultsThe incidence of acute toxicities like oral mucositis, dysphagia, nausea, vomiting, and leukopenia were much less in cetuximab arm and statistically significant difference was observed as compared to cisplatin arm. and no major systemic toxicities were encountered in the cetuximab arm.ConclusionWeekly cetuximab with concurrent radiotherapy in locally advanced HNSCC is a promising regimen with well tolerable toxicity profile. Larger prospective randomized studies with a longer duration of follow-up with direct comparison of both the regimens are needed for strong evaluation of efficacy and toxicity profile.

Concurrent high-dose intensity-modulated radiotherapy and chemotherapy for unresectable locally advanced and metastatic pancreatic cancer: a pilot study

AbstractAim:To evaluate the efficacy of concurrent chemotherapy and high-dose (≥55 Gy) intensity-modulated radiotherapy (CCIMRT) in comparison with chemotherapy alone and intensity-modulated radiotherapy (IMRT) alone for unresectable locally advanced or metastatic pancreatic cancer.Methods:Forty-six patients with pancreatic cancer undergoing CCIMRT (n = 17), chemotherapy alone (n = 16) or IMRT alone (n = 13) were analysed. Overall survival (OS), locoregional progression-free survival (LRPFS) and gastrointestinal toxicities were evaluated. The median radiation dose was 60 Gy (range, 55–60) delivered in a median of 25 fractions (range, 24–30). Gemcitabine (GEM) alone, GEM + S-1, S-1 alone, FOLFIRINOX and GEM + nab-paclitaxel were used in CCIMRT and chemo-monotherapy.Results:The 1-year OS rate was 69% in the CCIMRT group, 27% in the chemotherapy group and 38% in the IMRT group (p = 0·12). The 1-year LRPFS rate was 73, 0 and 40% in the 3 groups, respectively (p = 0·012). Acute Grade ≥ 2 gastrointestinal toxicity (nausea, diarrhea) was observed in 12% (2/17) in the CCIMRT group, 25% (4/16) in the chemotherapy group and 7·7% (1/13) in the IMRT group (p = 0·38). Late Grade 3 gastrointestinal bleeding was observed in 6·3% (1/16) in the chemotherapy group.Conclusion:High-dose CCIMRT yielded acceptable toxicity and favorable OS and LRPFS.

The effect of adding concurrent chemotherapy to radiotherapy for stage II nasopharyngeal carcinoma with undetectable pretreatment Epstein-Barr virus DNA: Retrospective analysis with a large institutional-based cohort

Little is known about the value of adding concurrent chemotherapy (CC) to radiotherapy for stage II nasopharyngeal carcinoma (NPC) with undetectable (0 copies/mL) pretreatment Epstein-Barr Virus (EBV) DNA in the intensity-modulated radiotherapy (IMRT) era. To address this question, the present study retrospectively reviewed 514 patients with newly diagnosed stage II NPC and undetectable pretreatment EBV DNA from Sun Yat-sen University Cancer Center between March 2008 and October 2016. Clinical characteristics and survival outcomes between concurrent chemoradiotherapy (CCRT) and IMRT alone groups were compared. Propensity score matching analysis was conducted to control for confounding factors. Although CCRT group had significantly higher proportions of stage N1 disease than IMRT alone group before matching (85% vs. 61%, p < 0.001), no statistically significant differences were noted for OS (97.8% vs. 98.1%, p = 0.700), DFS (93.4% vs. 94.5%, p = 0.846), DMFS (96.0% vs. 96.9%, p = 0.762), and LRFS (97.3% vs. 98.1%, p = 0.701). After 1:1 propensity-score matching, 177 pairs were identified. Patients in each group were found to be well balanced in baseline characteristics and risk factors (all P > 0.05). The five-year OS (96.9% vs. 98.2%, p = 0.302), DFS (92.0% vs. 95.2%, p = 0.777), DMFS (95.2% vs. 97.6%, p = 0.896), and LRFS (97.3% vs. 97.6%, p = 0.328) rates remain comparable for both CCRT and RT alone groups. Additionally, subgroup analysis still failed to observe any significant survival benefit for the addition of CC to IMRT for N1 disease (P>0.05 for all). Our results indicated that IMRT alone appeared to achieve comparable survival to CCRT for stage II NPC with undetectable pretreatment EBV DNA.

Predictors of Severe Lymphopenia During Chemoradiation Therapy for Anal Cancer

Purpose/Objective(s): Lymphopenia has been associated with poorer outcomes in multiple solid malignancies, including anal squamous cell carcinoma (ASCC). Lymphopenia is particularly important in the setting of chemoradiation (CRT) for ASCC given the trials underway to evaluate the potential role of immunotherapy in localized anal cancer. This study looks to identify clinical, tumor, and dosimetric factors that predict for severe lymphopenia during CRT for ASCC. Materials/Methods: Patients diagnosed with anal canal or anal margin squamous cell carcinoma from 2016-2019 and treated with CRT at our Cancer Institute/Department of Radiation Oncology were identified. Only patients who received 5-fluorouracil and mitomycin C (5FU/MMC) chemotherapy with concurrent intensity modulated radiation therapy (IMRT) to 50.4-59.4 Gy with definitive intent were included in this analysis. Charts and lab results were reviewed and absolute lymphocyte count (ALC) nadir during CRT was recorded. Those with ALC nadir < 0.2 x 109/L were identified as having Grade 4 lymphopenia. Multivariable logistic regression analysis was used to develop a prediction model for Grade 4 lymphopenia. Factors analyzed included age, gender, BMI, HIV status, history of prior malignancy, pretreatment ALC, T-stage, nodal status, group stage, PTVa volume, PTV total volume, radiation prescription dose, volume of iliac crest receiving 30 Gy (iliac crest V30), 40 Gy, (V40), and 50 Gy (V50), and overall radiation plan hotspot. A total of 51 patients treated with definitive 5FU/MMC and IMRT were identified. The mean age was 61 years. Forty-three (84%) were women and 8 (16%) were men. The median BMI was 27. Three patients had a known diagnosis of HIV and 3 had a history of prior malignancy. Fourteen percent of patients had Stage I, 31% had Stage II, 53% had Stage III, and 2% had oligometastatic stage IV disease. Median prescribed radiation dose was 54 Gy. Thirty patients (59%) developed Grade 4 lymphopenia during the course of CRT. On univariable logistic regression, T-stage, nodal status, PTVa volume, PTV total volume, radiation prescription dose, iliac crest V40, iliac crest V50, and radiation plan hotspot were associated with Grade 4 lymphopenia. On multivariable logistic regression iliac crest V40 (p = 0.03) predicted for Grade 4 lymphopenia with an odds ratio of 1.7. The mean iliac crest V40 was 11%. Dose to the iliac crests is an independent predictor for severe lymphopenia during definitive CRT for anal cancer. The use of predictors to identify patients at risk for severe lymphopenia will be increasingly important as interest in immunotherapy in the treatment of ASCC expands.

Pericardial effusion after definitive concurrent chemotherapy and intensity modulated radiotherapy for esophageal cancer

BackgroundThe literature regarding pericardial effusion after definitive concurrent chemotherapy and intensity modulated radiotherapy (IMRT) for esophageal cancer was lacking. This study aimed to investigate the risk factors of pericardial effusion in esophageal cancer patients undergoing definitive concurrent chemotherapy and IMRT.MethodsA total of 126 consecutive esophageal cancer patients treated with definitive concurrent chemotherapy and IMRT between 2008 and 2018 were reviewed. The pericardial effusion was determined on computed tomography scan of the chest and graded by the Common Terminology Criteria for Adverse Events, version 4.0. The cumulative incidence of pericardial effusion was estimated by the Kaplan–Meier method and compared between groups by the log-rank test. The risk factors of pericardial effusion were determined with multivariate Cox proportional hazards regression analysis.ResultsThe median follow-up time was 14.0 months. Thirty-seven (29.4%) patients had pericardial effusion after a median interval of 6.6 months since the end of IMRT. The cumulative incidence of pericardial effusion of any grade was higher in patients with mean heart dose > 23.45 Gy (p = 0.00018), heart V30 > 33.55% (p = 0.00015), mean pericardium dose > 20.33 Gy (p = 0.00027), and pericardium V20 > 42.55% (p = 0.00018). Furthermore, eight (6.3%) patients had symptoms related to pericardial effusion and were considered as cases with pericardial effusion ≥ grade 3. The cumulative incidence of pericardial effusion ≥ grade 3 was higher in patients with pericardium V30 > 65.80% (p = 0.00028), V40 > 55.35% (p < 0.0001), and V60 > 24.70% (p = 0.0021). Multivariate analyses showed the above dose-volume parameters predicted the risk of pericardial effusion in esophageal cancer.ConclusionsDose-volume parameters predicting the risk of pericardial effusion were identified in esophageal cancer treated with definitive concurrent chemotherapy and IMRT. They could be applied as constraints of IMRT for esophageal cancer.

Influence of concurrent chemotherapy on locoregionally advanced nasopharyngeal carcinoma treated with neoadjuvant chemotherapy plus intensity-modulated radiotherapy: A retrospective matched analysis

Neoadjuvant chemotherapy (NAC) combined with intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy (CC) will be the new standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) patients. However, many patients fail to receive CC for multiple reasons. We aimed to investigate long-term survival outcomes and toxicities in these patients with NPC treated with additional NAC plus concurrent chemoradiotherapy (CCRT) or IMRT alone. In total, 1,378 previously untreated, newly diagnosed locoregionally advanced NPC patients receiving NAC plus IMRT with or without CC were retrospectively reviewed. We used a propensity score-matched (PSM) method with 1:1 matching to identify paired patients according to various covariates. Survival outcomes and toxicities were compared between the two groups. In total, 288 pairs were identified. With a median follow-up of 86 (range: 8–110) months, the estimated 5-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival (PFS), and overall survival rates in patients treated with NAC plus CCRT vs. NAC plus IMRT alone were 96.1% vs. 94.7% (P = 0.201), 93.7% vs. 89.8% (P = 0.129), 91.3% vs. 85.1% (P = 0.024), and 93.0% vs. 90.6% (P = 0.362), respectively. Multivariate analysis showed that CC omission was a prognostic factor for worse PFS. In a subgroup analysis, PFS did not differ significantly between two groups of female patients or aged <60 years or stage T1–2 or stage N0-1 disease. However, fewer acute complications were observed in the NAC plus IMRT alone group. NAC with IMRT alone confers similar survival rates and less acute toxicities. Specifically, NAC plus IMRT alone may be enough for female patients <60 years with stage T1-2 or stage N0-1. However, a prospective randomised trial is needed to validate these results.

Administration of nimotuzumab combined with cisplatin plus 5-fluorouracil as induction therapy improves treatment response and tolerance in patients with locally advanced nasopharyngeal carcinoma receiving concurrent radiochemotherapy: a multicenter randomized controlled study

BackgroundNimotuzumab (NTZ) is an anti-EGFR monoclonal antibody. However,the effect of targeted drugs combined with induction therapy in locally advanced nasopharyngeal carcinoma remains unclear. The aim of this study is to investigate the safety and efficacy of NTZ combined with cisplatin plus 5-fluorouracil (PF) as induction regimen in locally advanced nasopharyngeal carcinoma (NPC) patients receiving concurrent radiochemotherapy.MethodsThis was a multicenter randomized controlled study performed in eight Guangxi hospitals in 2015–2017. Eligible patients with NPC were randomized into nimotuzumab/PF (NPF group) and docetaxel/PF (DPF group) regimens, respectively, as induction therapy. After 2 cycles of induction therapy, all patients received cisplatin and concurrent intensity modulated radiation therapy (IMRT). Then, the two groups were compared for safety and efficacy.ResultsA total of 118 patients with stage III-IVa NPC were assessed, with 58 and 60 in the NPF and DPF groups, respectively. Compared with DPF treatment, NPF induction therapy showed a more pronounced effect on cervical lymph nodes (P = 0.036), with higher response rate (RR) (81% vs 60%). Compared with the DPF group, the NPF group showed significantly reduced leukopenia, neutropenia and gastrointestinal reactions (all P < 0.05); rash only appeared in the NPF group, but all cases were grade 1. During concurrent treatment with radiotherapy and chemotherapy, the NPF group showed better tolerance to radiotherapy and chemotherapy; neutropenia, anemia, gastrointestinal reactions, oral mucositis and radiation dermatitis in the NPF group were significantly reduced (P < 0.05). The expression rate of EGFR was 94.9% (112/118). Compared with the DPF group, patients with EGFR expression in the NPF group showed better response (77.8% vs 63.0%, P = 0.033).ConclusionFor locally advanced NPC patients receiving follow-up cisplatin and IMRT, nimotuzumab/PF for induction therapy has better lymph node response rate and milder adverse reactions than the DPF regimen. In addition, the patients have better tolerance in subsequent concurrent radiotherapy and chemotherapy; however, long-term efficacy needs further follow-up evaluation.Trial registrationThe registration number of the clinical trial is ChiCTR-OIC-16008201 and retrospectively registered on March 31, 2016.

Induction Therapy of Nituzumab Combined PF Regimen to Improve the Treatment Response and Tolerance of Locally Advanced Nasopharyngeal Carcinoma Undergoing the Concurrent Chemoradiotherapy: A Multi-Center Controlled Randomized Clinical Study

The role of targeted combined with chemotherapy-based induction therapy in locally advanced nasopharyngeal carcinoma with concurrent intensity-modulated radiotherapy(IMRT) is unclear. Through a multi-center randomized controlled study to investigate the safety and efficacy of the induction therapy of nimotuzumab combined with PF regimen (cisplatin + 5-fluorouracil) in the follow-up treatment of locally advanced nasopharyngeal carcinoma patients received concurrent chemoradiotherapy. From January 2015 to November 2017，We included 118 patients with stage III-IVa nasopharyngeal carcinoma from 8 tumor centers, 58 cases in NPF group (induction therapy of nimotuzumab combined with PF regimen) and 60 cases in TPF group (induction chemotherapy of docetaxel, cisplatin and fluorouracil regimen). After two cycles of induction therapy, all patients received cisplatin concurrent intensity-modulated radiotherapy (IMRT), and the safety and short-term efficacy of the two groups were compared. To analyze the correlation between the curative effect of induction therapy and EGFR expression. Until May 2018, all patients were treated and evaluated immediately after treatment. Compared with the TPF regimen , the nimotuzumab combined PF scheme was more effective for the cervical lymph node (p=0.036), and the response rate (CR+PR) was higher (60% vs 81%) , but there was no statistically significant difference in the curative effect of nasopharyngeal lesion and induction therapy (p=0.446,p=0.143); there was no statistically significant difference in immediate curative effect (p=0.449). Compared with the TPF group, although the incidence of 1 grade rash was significantly increased (p=0.012), the neutropenia and gastrointestinal reaction of NPF group was significantly reduced, the difference was statistically significant (p=0.028;p=0.049).The treatment tolerance of cisplatin during the IMRT stage is better in the NPF group, the gastrointestinal reaction, oral mucositis and radiation dermatitis were significantly reduced, and the difference was statistically significant (p=0.038,p=0.041,p=0.035).The expression rate of EGFR in the whole group was 94.9%. Compared with chemotherapy, patients with EGFR high expression can get a better treatment response (P=0.033) from the induction treatment of nituzumab monoclonal combined chemotherapy. For the locally advanced nasopharyngeal carcinoma patients received treated with cisplatin concurrent IMRT, the induction therapy of nimotuzumab combined with PF regimen has a better lymph node remission rate and mild adverse reactions. Patients had better tolerance in subsequent concurrent chemoradiochemotherapy , but the long-term efficacy requires further follow-up observation. Patients with EGFR high expression may gain more benefits from the induction treatment of EGFR combined chemotherapy.

A phase II multicenter randomized controlled trial to compare standard chemoradiation with or without recombinant human endostatin injection (Endostar) therapy for the treatment of locally advanced nasopharyngeal carcinoma: Long-term outcomes update

Purpose: This study aimed to observe the feasibility and safety of addition of recombinant human endostatin injection to standard chemoradiation for the locally advanced nasopharyngeal carcinoma. Current follow-up results updated long-term efficacy and late toxicity of the trial.Methods: Between July 2012 and December 2013, we enrolled 114 patients that are older than 18 years with stage Ⅲ-Ⅳb nasopharyngeal carcinoma from 3 centers in Guizhou, China. Fifty six patients who received standard chemoradiation combined with recombinant human endostatin injection (Endostar) were included in the study group. Another 58 patients were randomly assigned to the control group without using Endostar. Patients in both groups received the same 2 cycles of induction chemotherapy (Docetaxel 75 mg/m2, cisplatin 80 mg/m2), followed by 2 cycles of concurrent intensity-modulated radiation therapy with cisplatin (DDP; 80 mg/m2 on days 1 and 22). The patients in the experimental group received 2 cycles Endostar (7.5 mg/m2 d8-d21 during induction chemotherapy and d1-d14 during concurrent chemoradiation).Results: There were no significant differences of toxicities between the 2 groups. Chemotherapy and radiotherapy compliance between the 2 groups was similar. No hemorrhage and coagulation dysfunction in the experimental group were observed. There was a median follow-up of 67.1 months. Comparing the short-time effect of 3 months to the completion of chemoradiotherapy, there was a little higher objective response rate in the experimental group. Compared with the control group, the experimental group improved in the complete remission rate of cervical lymph node metastasis (91.1% vs 72.4%, χ2 = 3.897, P = 0.048). However, there was no significant difference in the curative effect of nasopharyngeal lesions between the 2 groups. (78.6% vs 74.1%, χ2 = 0.310, P = 0.578). The 5-year overall survival, progression-free of survival, metastasis-free survival, and locoregional failure-free survival rates in the 2 groups were 69.6%, 67.8%, 78.75, and 83.0%, respectively, for the experimental group, these rates were 73.2%, 80.1%, 81.7%, and 91.0%, respectively, and for the control group, no significant difference was found (P > 0.05).Conclusions: Patients show good tolerance and compliance with a manageable toxicity profile to the regimen of chemoradiation plus Endostar. There was a little higher objective response rate in the study group. A phase 3 randomized study is needed to substantiate our findings.

Safety and efficacy of nimotuzumab and concurrent intensity-modulated radiation therapy and chemotherapy for locally advanced cervical squamous cell cancer.

5532 Background: To evaluate the safety and efficacy of nimotuzumab plus concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy for the treatment of locally advanced cervical squamous cell cancer (LACSCC). Methods: From December 2013 to March 2017, 31 patients with stage (FIGO 2009) IB2-IVA cervical squamous cell cancer were enrolled in this single-arm clinical trial at an academic medical center and received concurrent chemoradiotherapy plus nimotuzumab. All patients underwent at least 1 year of follow-up. The prescription radiation dose was 50.4 Gy/28 F on the pelvic field with or without extended-field radiation. An additional 30-36 Gy to Point A was delivered with high-dose-rate techniques. Cisplatin 40 mg/m2 and nimotuzumab 200 mg were infused intravenously once weekly during radiotherapy. The main and secondary outcome measures were toxicity evaluated using CTCAE 4.0., and the short-term outcome evaluated by RECIST 1.1. Results: The median follow-up duration was 29.7 months (13.3-61.2 months). All patients received external beam radiotherapy, brachytherapy, and nimotuzumab six times. Twenty-seven patients received six cycles of chemotherapy while four received only 4-5 cycles. There was no life-threatening toxicity. The incidence of acute grade 3 bone marrow depression was 51.6% (16/31) and grade 3 gastrointestinal tract reaction was 9.7% (3/31). The incidence of late toxicities was 22.6% (7/31), and these included vaginal-rectal fistula, intestinal obstruction, rectal hemorrhage, hematuria, and vaginal stenosis. Complete response was achieved in 30 cases (96.8%). The 1-year disease-free survival (DFS), local progression-free survival (LPFS), and overall survival (OS) rates were 87.1%, 90.3%, and 100%, respectively. The corresponding 3-year values were 74.8%, 90.3%, and 86.7%. Conclusions: Nimotuzumab plus concurrent IMRT and chemotherapy may represent a well-tolerated and effective treatment regimen in patients with LACSCC.

Development of a clinicomolecular risk stratification system for nonmetastatic nasopharyngeal carcinoma using Epstein–Barr virus DNA and TNM stage: A “Big data” analysis of 9,160 endemic cases.

6043 Background: To construct a clinicomolecular index integrating circulating Epstein-barr virus (cfEBV) DNA with T- and N- categories for better prognostication in nasopharyngeal carcinoma (NPC). Methods: Clinical and treatment records of 9,160 biopsy-proven, non-metastatic NPC cases were identified from an institutional “Big-data” platform. Decision tree modeling (DTM), recursive partitioning analysis (RPA) and adjusted hazard ratio (AHR) methods were used to generate clinicomolecular risk models. Outcome prediction of the models were compared against 8th edition TNM stage and two RPA-original models. Results: We observed linearity between cfEBV DNA and DFS; cfEBV DNA of &gt; 2,000 copies was consistent for risk discretisation (HR &gt; 1.0) for DFS, OS and DMFS in our cohort of 9,160 patients. DTM, RPA-new and AHR modelling using a two-tiered stratification by cfEBV DNA (≤2,000 and &gt; 2,000 copies) and T- and N- categories yielded five risk groups with significantly disparate DFS (P &lt; 0.001 for all subgroup comparisons). AHR model outperformed all other models and the TNM stage classification with better hazard consistency, hazard discrimination, explained variation, sample size balance and likelihood difference. Importantly, our clinicomolecular AHR groupings were significantly associated with the efficacy of different therapeutic regimes. Outcomes were comparable between concurrent chemoradiotherapy and intensity-modulated radiotherapy (IMRT) and IMRT alone for AHR1-2 (3-y DFS [AHR1] = 96.2% [IMRT] vs 95.3% [chemo-IMRT]; 3-y DFS [AHR2] = 91.1% vs 90.4%). Neoadjuvant chemotherapy and chemo-IMRT was superior to chemo-IMRT alone for AHR4-5 (AHRDFS 0.77[0.65-0.93], P = 0.005; 0.77[0.61-0.97], P = 0.027), but not for AHR3 (AHRDFS 1.07[0.86-1.34]). Conclusions: Here, we present a robust clinicomolecular risk stratification system that outperforms the TNM stage classification in non-metastatic NPC. Our clinicomolecular model is associated with the efficacy of different therapeutic regimes.