Concurrent Chemoradiotherapy In Patients Research Articles

Concurrent chemoradiotherapy for cervical cancer in a single institution: High-dose rate brachytherapy vs helical tomotherapy

Objective: We reviewed our experience and evaluated the results of helical tomotherapy (HT) compared the disease outcome with that of high-dose rate brachytherapy in patients with cervical cancer. Methods: Total 114 patients who have been treated with concurrent chemoradiotherapy(CCRT) for newly diagnosed cervical cancer from 2008 to 2017 were retrospectively reviewed. Radiotherapy was given as a combination of whole pelvic external beam RT (EBRT) followed by high-dose rate brachytherapy(BT) or helical tomotherapy(HT). Results: We extracted selected population using propensity score matching with 1:1 ratio. After adjustment for age, BMI, radiation dose, prior surgery, clinical stage and histologic type, there was no significantly different parameter between two groups. The overall survival was poorer in BT group compared to HT group (median survival 17.5 months after BT vs 30 months after HT, log rank p=0. 034). 4-year survival rates were 74.2% in brachytherapy group and 100% in tomotherapy group. But the progression free survival was not different between two groups(p=0.270). 1-year and 2-year progression-free rates were 85.3% and 76.3% in BT group, but those were 87.0% and 58.9% in HT group. In univariate analysis, there was no significant risk factor for overall survival. But in PFS, stage was the only significant risk factor for recurrence. In multivariate analysis, clinical stage was still significant risk factor after adjusting for the other clinical parameters. Conclusion: HT could be a feasible option for CCRT in patients with cervical cancer with appropriate indications. Further studies with delicate design and larger number from multicenter with long follow up period are warranted to confirm the significance of benefit of HT in concurrent chemoradiotherapy in the field of cervical cancer.

Characterization of the tumor immune micromilieu and its interference with outcome after concurrent chemoradiation in patients with oropharyngeal carcinomas

ABSTRACT Background: Intra-tumoral CD8 + T-cell infiltration in squamous cell carcinoma of the head and neck (HNSCC) has previously been linked to the efficacy of cisplatin-based chemoradiation (CDDP-CRTX) and immune checkpoint inhibitor (ICI) monotherapy. Further detailed characterization of the tumor immune-micromilieu and its influence on outcome may guide the development of CRTX-ICI combinations. Methods: Comprehensive immune transcriptome analysis was applied to a training set of tumor specimens from oropharyngeal squamous cell carcinoma (OPSCC) patients treated with CDDP-CRTX in the ARO-0401 phase III study (n = 33). A composite immune signature risk score (ISRS) for survival prediction was developed, and subsequently validated in two independent OPSCC cohorts treated with either CDDP-CRTX (n = 36) or mitomycin-based CRTX (MMC-CRTX, n = 31). Further validation of the ISRS was performed in the OPSCC subset (n = 79) of the TCGA HNSCC cohort. Potential interference between immune signatures and HPV status was evaluated in multivariate Cox regression models. Results: Significant differences according to the 3-y OS status in the abundance of tumor-infiltrating T- and B-cells, and the expression levels of 51 immune-related genes were observed. A risk score based on 13 differentially expressed genes involved in cytokine signaling, T-cell effector functions and the TNFR pathway was established as robust predictive factor of OS. Its predictive power was superior to the 6-gene interferon-gamma signature of ICI efficacy and independent of the HPV status. Conclusions: This study further elucidates the complex interaction of the tumor immune microenvironment with the efficacy of CDDP-CRTX in OPSCC. The results suggest immune markers for selection of patients treated with CRTX-ICI combinations.

Phase II study of consolidation amrubicin after concurrent chemoradiotherapy for patients with limited-stage small cell lung cancer.

8555 Background: Concurrent chemoradiotherapy (CCRT) using etoposide and cisplatin has been the gold standard for limited-stage small-cell lung cancer (LS-SCLC) for decades; however, approximately three out of four cases treated by CCRT inevitably relapse. Amrubicin (AMR), a synthetic anthracycline with a structure similar to doxorubicin, has demonstrated strong antitumor activity against relapsed SCLC and has been the standard second-line treatment for SCLC in Japan. We consider consolidation AMR following CCRT to be a potential treatment for patients with LS-SCLC. Methods: In this single-arm, multicenter phase II study, all patients enrolled were treated using induction CCRT consisting of four cycles of etoposide at 100 mg/m2 on days 1-3 and cisplatin at 60 mg/m2 on day 1 every 3 weeks, plus concurrent thoracic radiotherapy (1.5 Gy twice daily, total 45 Gy) concomitant with the first cycle of chemotherapy. Then, eligible patients received three cycles of AMR at 40 mg/m2 on days 1-3 every 3 weeks as consolidation treatment. The primary endpoint was the 2-year progression-free survival (PFS) rate in patients who received consolidation AMR, and the secondary endpoints were objective response rate (ORR), PFS, overall survival (OS), and safety. This study was terminated early due to slow patient accrual. Results: Of the 36 patients who underwent induction CCRT (ITT population), 28 (78%) received AMR as consolidation therapy (consolidation population) and 24 (67%) completed all planned treatments. The 2-year PFS rate and ORR were 35.7% and 86% (8 CR and 16 PR), respectively, in the consolidation population. The median PFS and median OS were 14.3 months (95%CI, 10.8-46.6) and 60.9 months (95%CI, 29.8-NR), respectively, in the consolidation population. In the ITT population, the median PFS and the median OS were 13.4 months (95%CI, 7.5-19.0) and 60.9 months (95%CI, 29.8-NR), respectively. Grade 3/4 toxicities during the consolidation phase included neutropenia (39%), thrombocytopenia (14%), and febrile neutropenia (7%). There were no treatment-related deaths in the ITT population. Conclusions: Consolidation AMR following standard CCRT consisting of etoposide and cisplatin plus concurrent thoracic radiotherapy was feasible, and demonstrated promising efficacy for LS-SCLC. Clinical trial information: 000002352.

Endoscopic Submucosal Dissection Followed by Concurrent Chemoradiotherapy in Patients with Early Esophageal Cancer with a High Risk of Lymph Node Metastasis

Endoscopic submucosal dissection is recommended as an alternative therapy for early esophageal cancer. However, achieving curative resection in this procedure remains controversial since precise prediction of lymph node metastasis can be difficult. Here, we present the preliminary results of endoscopic submucosal dissection followed by concurrent chemoradiotherapy for early esophageal cancer with a high risk of lymph node metastasis. From May 2006 to January 2014, six patients underwent concurrent chemoradiotherapy after endoscopic submucosal dissection with a median follow-up period of 63 months. No complications were encountered during concurrent chemoradiotherapy. Although local recurrence did not occur in all patients, two patients were diagnosed with metachronous cancer. Overall, the survival rate was 100%. Thus, endoscopic submucosal dissection followed by concurrent chemoradiotherapy may be a feasible treatment for early esophageal cancer in patients with a high risk of lymph node metastasis. Future prospective large-scale studies are warranted to confirm our results.

RAD18 may function as a predictor of response to preoperative concurrent chemoradiotherapy in patients with locally advanced rectal cancer through caspase-9-caspase-3-dependent apoptotic pathway.

Neoadjuvant chemoradiotherapy (nCRT) has been widely applied to improve the local control rate and survival rate in patients with locally advanced rectal cancer (LARC), yet only part of LARC patients would benefit from nCRT. Therefore, it is imperative to predict the therapeutic outcome of nCRT. Here, we showed that RAD18, an E3 ubiquitin‐linked enzyme, played a fundamental role in predicting the response of LARC patients to nCRT. According to clinical data, patients with low RAD18 expression level in their pre‐nCRT biopsies had a superior response to nCRT compared to those with high RAD18 expression. Inhibition of RAD18 expression in rectal cancer cells pronouncedly attenuated the proliferation and promoted apoptosis after exposing to irradiation or/and 5‐fluorouracil (5‐Fu). Downregulated RAD18 levels increased cell apoptosis by activating caspase‐9‐caspase‐3‐mediated apoptotic pathway, thus resulting in the enhancement of cell radiosensitivity and 5‐Fu susceptibility. Furthermore, a xenograft nude mouse model showed that silencing RAD18 significantly slowed tumor growth after irradiation or/and 5‐Fu in vivo. Collectively, these results implied that RAD18 could be a new biomarker to predict LARC patients who might benefit from nCRT and provide new strategies for clinical treatment of LARC.

Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II-IVB nasopharyngeal carcinoma: A cost-effectiveness analysis

BackgroundNedaplatin-based concurrent chemoradiotherapy became an alternative doublet treatment strategy to cisplatin-based concurrent chemoradiotherapy in patients with locoregional, advanced nasopharyngeal carcinoma. Materials and methodsUsing a Markov model, we simulated patients with nasopharyngeal carcinoma from disease-free to death. Input data for the model were collected from published literature and the standard fee database of West China Hospital. The outcome was expressed in quality-adjusted-years (QALYs), net monetary benefit at the threshold of $25,841, three times the Gross Domestic Product of China in 2017. The costs and benefits were discounted at 3% annually and a half-cycle correction was considered. The input parameters were varied in one-way sensitivity analysis to confirm the robustness of the model. All of the primary analyses used second-order probabilistic sensitivity analysis to capture the impact of parameter uncertainty based on 10,000 Monte-Carlo simulations. ResultsThe mean QALYs of treatment in stage II-IVB nasopharyngeal carcinoma were comparable: 2.90 QALYs for nedaplatin and 3.12 QALYs for cisplatin. Nedaplatin cost $34,505 compared with $27,167 for cisplatin, generating an incremental net monetary benefit of nedaplatin versus cisplatin of $-13,357 at the ceiling ratio of $25,841. The results of nedaplatin remained cost-ineffective over the majority of the sensitivity analyses. The cost-effectiveness curve showed that the probability of strategies being cost-effective were 0% for nedaplatin and 100% for cisplatin in stage II-IVB nasopharyngeal carcinoma at any willingness-to-pay threshold. ConclusionsNedaplatin is a dominated, cost-ineffective alternative to concurrent chemoradiotherapy in stage II-IVB nasopharyngeal carcinoma compared with cisplatin from the perspective of Chinese society.

67TiP - ADRIATIC: A phase III trial of durvalumab ± tremelimumab after concurrent chemoradiation for patients with limited stage small cell lung cancer

67TiP - ADRIATIC: A phase III trial of durvalumab ± tremelimumab after concurrent chemoradiation for patients with limited stage small cell lung cancer

The efficacy and safety of high dose versus standard dose radiotherapy in concurrent chemoradiotherapy for patients with esophageal squamous cell carcinoma

Objective: To compare the efficacy and treatment-related toxicity of high dose versus standard dose radiotherapy in concurrent chemoradiotherapy (CCRT) for patients with esophageal squamous cell carcinoma (ESCC). Methods: From 2005 to 2012, 183 pairs of patients with esophageal squamous cell carcinoma in the Fourth Hospital of Hebei Medical University were enrolled, all had undergone CCRT based on three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT). A propensity score was constructed to match the cohort. The overall survival (OS), local control (LC) probability, as well as the acute and late toxicities between standard-dose and high-dose groups were compared. Results: Patients in the high-dose group had significantly better OS and LC probability compared with those in the standard-dose group: the 3-, 5- and 10-year LC rate were 60.9%, 57.6%, 52.3% versus 50.8%, 46.4%, 30.8%, respectively (P=0.032). The 3-, 5- and 10-year OS were 44.3%, 36.9% and 24.5% for high-dose group, and 31.7%, 20.6% and 14.1% for the standard-dose group, respectively(P=0.002). The incidence of acute radiation esophagitis (especially in grade 2 and 3) was 63.9% in high-dose group, which was significantly higher than that in the standard-dose group (59.6%). Severe (≥ grade 3) late-onset esophagitis was observed in neither group. The grade 4 acute esophagitis was rare. There was no significant difference in the incidence of radiation pneumonitis, gastrointestinal reactions or hematological toxicities between the two groups. Six patients in high-dose group and two patients in standard-dose group experienced ≥ grade 4 leukocytopenia, while no one experienced > grade 3 thrombocytopenia and anemia in both group. Conclusions: 60 Gy was the preferred dosage of CCRT in patients with ESCC. Compared with standard-dose, the high-dose CCRT yielded slightly increased mild to moderate acute radiation esophagitis, while life-threatening toxicities were not increased.

Noninvasive Biomarker for Predicting Treatment Response to Concurrent Chemoradiotherapy in Patients with Hepatocellular Carcinoma

Noninvasive Biomarker for Predicting Treatment Response to Concurrent Chemoradiotherapy in Patients with Hepatocellular Carcinoma

Concurrent chemo-radiotherapy for unresectable non-small cell lung cancer invading adjacent great vessels on radiologic findings: is it safe?

We performed a retrospective analysis to evaluate treatment outcomes and the risk of fatal hemorrhage by tumor regression when definitive concurrent chemo-radiotherapy (CCRT) was delivered to patients with non–small cell lung cancer (NSCLC) invading adjacent great vessels on radiological findings. We selected 37 unresectable NSCLC patients with adjacent great vessel invasion (GVI) by carefully reviewing each patient’s images. The criteria of definite GVI were as follows: irregular indentation at the tumor–vessel contact border, slit-like narrowing of adjacent great vessels by the tumor, presence of intra-luminal mass formation, tumors contacting >5 cm of adjacent great vessel and obliteration of the intervening fat plane between tumor and adjacent great vessel, and/or tumors contacting more than half of the circumference of the aortic wall. All of the patients completed the CCRT, of which the median dose was 66.0 Gy (range, 59.4–72.0 Gy) with 1.8 or 2.0 Gy per fraction. The 2-year overall survival (OS) rate for total patients was 48.2%. Early nodal staging (P = 0.006) and good performance status (P = 0.044) were identified as independent prognostic factors associated with better OS. There was no fatal complication related to the GVI, such as a sudden death or massive hemoptysis due to vascular rupture after CCRT. We concluded that definitive CCRT for NSCLC patients with GVI on radiological findings has a low risk of fatal complication and it can benefit long-term survival when treated with CCRT in patients with early nodal staging or good performance status.

Long-term Survival After Surgery Compared With Concurrent Chemoradiation for Node-negative Small Cell Lung Cancer

To determine whether surgery with adjuvant chemotherapy offers a survival advantage over concurrent chemoradiation for patients with cT1-2N0M0 small cell lung cancer (SCLC). Although surgery with adjuvant chemotherapy is the recommended treatment for patients with cT1-2N0M0 SCLC per international guidelines, there have been no prospective or retrospective studies evaluating the impact of surgery versus optimal medical management for cT1-2N0M0 SCLC. Outcomes of patients with cT1-2N0M0 SCLC who underwent surgery with adjuvant chemotherapy or concurrent chemoradiation in the National Cancer Data Base (2003-2011) were evaluated using Cox proportional hazards analyses and propensity-score-matched analyses. During the study period, 681 (30%) patients underwent surgery with adjuvant chemotherapy and 1620 (70%) underwent concurrent chemoradiation. After propensity-score matching, all 14 covariates were well balanced between the surgery (n = 501) and concurrent chemoradiation (n = 501) groups. Surgery was associated with a higher overall survival (OS) than concurrent chemoradiation (5-year OS 47.6% vs 29.8%, P < 0.01). To minimize selection bias due to comorbidities, we limited the propensity-matched analysis to 492 patients with no comorbidities; surgery remained associated with a higher OS than concurrent chemoradiation (5-year OS 49.2% vs 32.5%, P < 0.01). In a national analysis, surgery with adjuvant chemotherapy was used in the minority of patients for early stage SCLC. Surgery with adjuvant chemotherapy for node-negative SCLC was associated with improved long-term survival when compared to concurrent chemoradiation. These results suggest a significant underuse of surgery among patients with early stage SCLC and support an increased role of surgery in multimodality therapy for cT1-2N0M0 SCLC.

Phase 2 Study of Radiation Therapy Plus Low-Dose Temozolomide Followed by Temozolomide and Irinotecan for Glioblastoma: NRG Oncology RTOG Trial 0420

To evaluate the toxicity and efficacy of adjuvant temozolomide (TMZ) and irinotecan (CPT-11) for 12months after concurrent chemoradiation in patients with newly diagnosed glioblastoma (GBM). Trial RTOG 04-20, a single-arm, multi-institutional phase 2 trial, was designed to determine the efficacy and toxicity of concomitant TMZ and radiation therapy (RT) followed by adjuvant TMZ combined with CPT-11 given for 12 cycles compared with historical controls of adjuvant TMZ alone given for 6 cycles. A total of 170 patients were enrolled, 152 of whom were eligible. Adjuvant CPT-11 combined with TMZ was more toxic than expected. A higher rate of hematologic and gastrointestinal toxicities was more frequently noted with the combination regimen compared with adjuvant TMZ alone. Grade 3/4 hematologic toxicity was 38% compared with 14% reported in the Stupp trial. After an early interim analysis, the adjuvant CPT-11 dose was reduced to 100mg/m2 on days 1 and 5 for the first cycle. CPT-11 dose escalation proceeded over the first 3 cycles if tolerated. Median overall survival for all eligible patients was 16.9months compared with 13.7months of the historical control (P=.03). Post hoc subgroup analysis suggested an improvement in overall survival for patients with Radiation Therapy Oncology Group recursive partitioning analysis class 3, although improvement was limited to 22 patients (14% of eligible patients). Although irinotecan and TMZ for 12 cycles given after chemoradiation for patients with newly diagnosed glioblastoma significantly improved median survival compared with historical control data at the time the study was conducted, the historical control median survival time of 13.7months does not represent the current benchmark for this patient population. Treatment intensification does prolong overall survival compared with the current standard.

Famitinib in combination with concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 1, open-label, dose-escalation Study

BackgroundFamitinib is a tyrosine kinase inhibitor against multiple targets, including vascular endothelial growth factor receptor 2/3, platelet-derived growth factor receptor, and stem cell factor receptor (c-kit). Previous studies have demonstrated anti-tumour activities of famitinib against a wide variety of advanced-stage solid cancers. We aimed to determine the safety and efficacy of famitinib with concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We also evaluated the feasibility of contrast-enhanced ultrasound (D-CEUS) as a predictor of early tumour response to famitinib and to correlate functional parameters with clinical efficacy.MethodsThe trial was conducted in subjects with stage III or IVa-b NPC using a 3 + 3 design of escalating famitinib doses. Briefly, subjects received 2 weeks of famitinib monotherapy followed by 7 weeks of famitinib plus CCRT. D-CEUS of the neck lymph nodes was performed at day 0, 8 and 15 after famitinib was administered before starting concurrent chemoradiotherapy. End points included safety, tolerability and anti-tumour activity.ResultsTwenty patients were enrolled (six each for 12.5, 16.5 and 20 mg and two for 25 mg). Two patients in the 25 mg cohort developed dose-limiting toxicities, including grade 4 thrombocytopenia and grade 3 hypertension. The most common grade 3/4 adverse events were leukopenia, neutropenia and radiation mucositis. D-CEUS tests showed that more than 60% of patients achieved a perfusion parameter response after 2 weeks taking famitinib alone, and the parameter response was associated with disease improvement. In the famitinib monotherapy stage, three patients (15%) showed partial responses. The complete response rate was 65% at the completion of treatment and 95% 3 months after the treatment ended. After a median follow-up of 44 months, the 3-year progression-free survival (PFS) and distant metastasis-free survival were 70% and 75%, respectively. Subjects with a decrease of perfusion parameter response, such as peak intensity decreased at least 30% after 1 week of famitinib treatment, had higher 3-year PFS (90.9% vs. 44.4%, 95% CI 73.7%–100% vs. 11.9%–76.9%, P < 0.001) than those with an increase or a reduction of less than 30%.ConclusionsThe recommended famitinib dose for phase II trial is 20 mg with CCRT for patients with local advanced NPC. D-CEUS is a reliable and early measure of efficacy for famitinib therapies. Further investigation is required to confirm the effects of famitinib plus chemoradiotherapy.

P2.17-30 Serum Lipoprotein(A) Correlates with the Effect of Endostar Combined with Concurrent Chemoradiotherapy in Patients with Locally Advanced LSCC

P2.17-30 Serum Lipoprotein(A) Correlates with the Effect of Endostar Combined with Concurrent Chemoradiotherapy in Patients with Locally Advanced LSCC

Invasive Paget's disease of the vulva treated with a combination of surgery and concurrent chemoradiotherapy: A case report.

Invasive Paget's disease of the vulva (IP) is rare among patients with vulvar cancer. Radiation therapy and chemotherapy are not considered as radical, whereas surgical resection of the tumor with abdominal lymphadenectomy is highly invasive. Thus, more effective and less invasive treatments for IP are required. The present study reports a case of a 64-year-old woman with IP, who was treated with a combination of surgery and concurrent chemoradiotherapy (CCRT). The patient was diagnosed with IP with suspected lymph node metastases to the inguinal and pelvic lymph nodes, after having suffered from pruritus vulvae for 7 years. Following mapping biopsy, wide local excision, bilateral inguinal lymph node resection and laparoscopic pelvic lymphadenectomy were successfully performed. The vulva was reconstructed with a local fat flap. Postoperative pathological examination revealed metastases to the bilateral superficial inguinal and the left obturator and lateral suprainguinal lymph nodes. Adjuvant CCRT (whole pelvic irradiation, 50.4 Gy with weekly cisplatin, 40 mg/m2) was completed without notable complications. Therefore, laparoscopic pelvic lymphadenectomy may be useful in determining the irradiation field for adjuvant CCRT in patients with advanced IP.

A nomogram for predicting survival of patients with locally advanced pancreatic cancer treated with chemoradiotherapy

BackgroundWe developed a nomogram for predicting survival of patients with locally advanced pancreatic cancer (LAPC) after concurrent chemoradiotherapy (CRT) using 18F-flurodeoxyglucose-positron emission tomography (FDG-PET) parameters and CA 19-9 levels. MethodsBased on 426 patients with LAPC who received concurrent CRT between 2004 and 2015, we investigated significant prognostic factors for survival to build a nomogram, including the maximum standardized uptake value (SUVmax) and CA 19-9 levels. Predictive accuracy and discriminative ability were then measured. ResultsMedian progression-free survival and overall survival (OS) were 9.4 and 15.4 months, respectively, at a median 15-month follow-up. High-dose radiation (EQD2, ≥61 Gy), initial SUVmax <3.5 and CA 19-9 ≤400 U/mL, and surgical resection after CRT were significantly related to prolonged OS by multivariate analysis (p < 0.05). A nomogram model for OS was established and showed good calibration and acceptable discrimination (c-index 0.656). Using the nomogram, 3 different prognosis groups could be identified with a median OS of 25, 15, and 11 months (p < 0.001). ConclusionA nomogram was developed with high-dose radiation (EQD2, ≥61 Gy), initial SUVmax <3.5, CA 19-9 ≤400 U/mL, and surgical resection after CRT for patients with LAPC. This will help in clinical decision-making and in selecting patients for CRT.

Comparative effectiveness of concurrent chemoradiotherapy versus EGFR-tyrosine kinase inhibitors for the treatment of clinical stage IIIb lung adenocarcinoma patients with mutant EGFR.

BackgroundThe standard of care for fit locally advanced non‐small cell lung cancer (NSCLC) patients is concurrent chemoradiotherapy (CCRT). However, in a subset of patients with lung adenocarcinoma with mutant EGFR (LA‐mEGFR), the role of EGFR‐tyrosine kinase inhibitors (TKIs) is not clear. We compared CCRT versus TKIs for the treatment of stage IIIb LA‐mEGFR in a Taiwanese population.MethodsWe identified patients from the Taiwan Cancer Registry with good performance status at clinical stage IIIb LA‐mEGFR, diagnosed from June 2011 to December 2015 and treated with either TKIs or CCRT. Clinical covariables and survival status were also collected. The Cox regression method was used in the primary analyses and several propensity score methods and alternative study cohort definitions were used in additional analyses.ResultsWe compared the data of 177 TKI and 22 CCRT patients and found no statistically significant difference in overall (adjusted hazard ratio of death 0.71, 95% confidence interval 0.34–1.47) or lung cancer‐specific survival (hazard ratio 0.65, 95% confidence interval 0.31–1.35). The results of most additional analyses were insignificant.ConclusionIn this population‐based study from Taiwan with limited case numbers, no statistical difference in the survival outcomes of patients with clinical stage IIIb LA‐mEGFR treated with either EGFR‐TKIs or CCRT was determined. Further prospective studies are needed to clarify our findings.

Effect of Definitive Concurrent Chemo Radiotherapy in Patients with Inoperable Esophageal Squamous Cell Carcinoma - A Prospective Study

Effect of Definitive Concurrent Chemo Radiotherapy in Patients with Inoperable Esophageal Squamous Cell Carcinoma - A Prospective Study

Recombinant human granulocyte macrophage colony-stimulating factor for the prevention and treatment of oral mucositis induced by concurrent chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma

Objective To observe the effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the prevention and treatment of oral mucositis induced by concurrent chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma. Methods A total of 64 patients with locally advanced nasopharyngeal carcinoma from April 2015 to April 2017 in the Second Affiliated Hospital of Xi'an Jiaotong University were enrolled. The patients were randomly divided into the observation group (32 cases) and the control group (32 cases) according to the random number table method. Both groups were treated with intensity modulated radiotherapy (IMRT) and synchronized with TP regimen (docetaxel + cisplatin) chemotherapy for 2 cycles. Both groups were treated with mouthwash at the beginning of radiotherapy to prevent oral mucositis. The observation group was given rhGM-CSF mouthwash, and the control group was given compound borax mouthwash. The oral mucositis and the oral pain during the treatment and the end of the treatment were evaluated by using American Radiation Oncology Group (RTOG)grading criteria and visual analogue scoring method (VAS) grading criteria. The time of onset of oral mucositis and the total time of radiotherapy in both groups was also recorded. Results All the patients were treated with concurrent chemoradiotherapy. The total radiotherapy time in the observation group was less than that in the control group [(46.4±1.6) vs. (48.2±3.2) d, t=-2.720, P=0.009]. The clinical total effective rate was 93.8% (30/32) in the observation group and 96.9% (31/32) in the control group respectively (χ 2=0.35, P = 0.554). The occurrence of grade 1, 2 and 3 oral mucositis in the observation group was (20.9±2.5), (29.3±2.4), and (34.5±1.8) d respectively, which was latter than that in the control group [(16.3±2.0), (24.2±2.2) and (31.0±2.2) d] respectively (t = 8.125, P = 0.000; t = 8.840, P = 0.000; t = 6.944, P = 0.001). During concurrent chemoradiotherapy, the incidence of grade 3 oral mucositis in the observation group was lower than that in the control group [31.2% (10/32) vs. 56.2% (18/32); Z = -2.197, P = 0.028]. At the end of concurrent chemoradiotherapy, the total incidence of grade 2 and grade 3 oral mucositis in the observation group was lower than that in the control group [53.1% (17/32) vs. 81.2% (26/32); Z = -2.708, P = 0.007]. The incidence of moderate and severe oral pain caused by oral mucositis in the observation group was lower than that in the control group [46.9% (15/32) and 6.2% (2/32) vs. 59.4% (19/32) and 15.6% (5/32), respectively; Z = -2.009, P = 0.045]. Conclusion rhGM-CSF mouthwash can delay the occurrence of oral mucositis, reduce the incidence of oral mucositis and oral pain to effectively prevent and treat oral mucositis induced by concurrent chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma, which is worthy of clinical application. Key words: Nasopharyngeal neoplasms; Radiotherapy; Antineoplastic combined chemotherapy protocols; Stomatitis; Granulocyte macrophage colony-stimulating factors, recombinant

Multicenter phase I/II study of chemoradiotherapy with high-dose CDDP for head and neck squamous cell carcinoma in Japan

ObjectiveRecent data indicated that concurrent chemoradiotherapy (CCRT) using high dose cisplatin (CDDP) is the most useful treatment for advanced head and neck squamous cell carcinoma (SCC). Regarding the dose of CDDP, 100mg/m2 is most recommended in Western countries. However, in terms of a balance of efficacy and adverse events, appropriate dose of cytotoxic drugs such as CDDP may be different among the different ethnic groups. In this multicenter phase I/II study, we aimed to identify the optimal dose of CDDP in CCRT for patients with advanced head and neck SCC in the Japanese. MethodsPatients were eligible for inclusion if they had head and neck SCC that was treated with radical CCRT comprising whole-neck irradiation of the primary lesion and level II–IV lymph nodes on both sides. For the phase I study, a CDDP dose was 70mg/m2 for level 0, 80mg/m2 for level 1, and 100mg/m2 for level 2. Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) were examined by phase I trial, by which CDDP dose for phase II was determined. The primary endpoint for the phase II was CCRT completion rate, and the secondary endpoint was full-dose-CCRT completion rate, the percentage of patients receiving a total CDDP dose of ≥200mg/m2, response rate, and incidences of adverse events. ResultsA CDDP dose of 100mg/m2 was the MTD for phase I, and the recommended dose for phase II was 80 mg/m2. Forty-seven patients were evaluated in the phase II trial. CCRT completion rate, full-dose-CCRT rate, and the percentage of patients receiving a total CDDP dose of ≥200mg/m2, were 93.6%, 78.7%, and 93.6%, respectively. One patient (2.1%) developed grade 2 renal dysfunction, and no patient developed febrile neutropenia or a grade 4 adverse event. ConclusionThe present phase I study indicated that a CDDP dose of 80mg/m2 is the optimal dose in terms of safety. The phase II study revealed that CCRT completion rate, response rate, and rates of adverse events were not inferior for a CDDP dose of 80mg/m2 as compared with a dose of 100mg/m2, and a dose of 80mg/m2 is therefore recommended in CCRT for the Japanese.This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; identification No. UMIN000010369).