Acute Mucositis Research Articles

Normal Tissue Complication Probability (NTCP) Modelling of Severe Acute Mucositis using a Novel Oral Mucosal Surface Organ at Risk

AimsA normal tissue complication probability (NTCP) model of severe acute mucositis would be highly useful to guide clinical decision making and inform radiotherapy planning. We aimed to improve upon our previous model by using a novel oral mucosal surface organ at risk (OAR) in place of an oral cavity OAR. Materials and methodsPredictive models of severe acute mucositis were generated using radiotherapy dose to the oral cavity OAR or mucosal surface OAR and clinical data. Penalised logistic regression and random forest classification (RFC) models were generated for both OARs and compared. Internal validation was carried out with 100-iteration stratified shuffle split cross-validation, using multiple metrics to assess different aspects of model performance. Associations between treatment covariates and severe mucositis were explored using RFC feature importance. ResultsPenalised logistic regression and RFC models using the oral cavity OAR performed at least as well as the models using mucosal surface OAR. Associations between dose metrics and severe mucositis were similar between the mucosal surface and oral cavity models. The volumes of oral cavity or mucosal surface receiving intermediate and high doses were most strongly associated with severe mucositis. ConclusionsThe simpler oral cavity OAR should be preferred over the mucosal surface OAR for NTCP modelling of severe mucositis. We recommend minimising the volume of mucosa receiving intermediate and high doses, where possible.

Outcome and long-term efficacy of four facio-cervical fields conformal radiotherapy for nasopharyngeal carcinoma.

PurposeTo evaluate the outcomes of 255 patients with nasopharyngeal carcinoma (NPC) treated with four facio-cervical fields conformal radiotherapy (4F-CRT).ResultsIn one patient's 3 different RT treatment modalities, the 4F-CRT techniques resulted in sharper of the dose-volume histograms (DVHs) for primary gross tumor volume (PGTVnx) and planning target volume (PTVnx), similar to the intensity modulated radiation therapy (IMRT). The median follow-up duration was 43 months. Locoregional relapse and distant metastases as the first treatment failure events occurred in 32 (32/255, 12.5%) and 20 (30/255, 11.8%) patients, respectively. The 3-year and 5-year local control, disease-free survival, and overall survival rates were 83.3%, 82%, 83.8%, and 76.1%, 73.2%, 76.3% respectively. Univariate analysis displayed that clinical stage, T-stage, N-stage, and tumor response were related to prognosis. Multivariate analysis indicated that age, T-stage, N-stage, and combined chemotherapy were independent prognosticators. The incidence of grade 1–2 acute mucositis and leukocytopenia were 93.7% and 91.0%, respectively, with no cases of grade 4 toxicity detected.Materials and MethodsFrom November 2007 to December 2011, 255 patients with histologically diagnosed, non-metastatic NPC were enrolled into this study and received 4F-CRT. Magnetic resonance imaging scans of the nasopharynx were performed on every patient. All patients received definitive radiotherapy with 6 MV X-rays using conventional fractions at 2 Gy daily, 5 fractions per week, and 231 patients with stage IIb-IV received concurrent chemotherapy and cisplatin-based adjuvant chemotherapy. The accumulated survival was calculated according to the Kaplan-Meier method; the log-rank test was used to compare survival differences. Multivariate analysis was performed using Cox's proportional hazard model.ConclusionsCompared with the conventional treatment plans, the 4F-CRT plan delivered more dose to cover the tumor volume and reduces the doses of the normal tissues including the parotid gland, TMJs and so on. The long-term efficacy of 4F-CRT is satisfactory and its toxicities are tolerable.

Bendamustine, Carfilzomib, and Melphalan (BCM) Conditioning Prior to Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma: A Feasibility Study

High-dose melphalan (M) followed by autologous hematopoietic stem cell transplantation (AHSCT) remains the standard treatment for multiple myeloma in eligible patients, even in the era of novel agents. However, the majority of patients ultimately relapse and succumb to their disease. Several studies have explored integrating novel agents into the conditioning regimen prior to AHSCT in order to improve complete remission rates and ultimately overall survival. We aimed to assess the feasibility of adding bendamustine (B) and carfilzomib (C) to melphalan (BCM) and performed a phase I dose escalation study. Thirteen patients were enrolled between June 2014 and June 2016. All patients received C at a fixed dose (20 mg/m2) on days (d) -29, -28, -22, -21, -15, -14. The conditioning regimen and doses administered for each cohort were as described in the table below. Due to excessive toxicity, the study was amended after the first 6 patients. Per oversight of a data safety monitoring board, the dose of M was reduced to 140 mg/m2 and C dose on d +6 was omitted. Median age was 58 years (39-68). There were 8 males and 5 females. Performance status was ≥ 80% in all patients. Per the International Staging System (ISS), 3 patients had stage I disease, 5 had stage II, 4 had stage III, and 1 had unknown staging. Three patients had high-risk cytogenetics: 2 with t(4;14) and 1 with deletion 17p. Three patients had received prior AHSCT. Disease status prior to study treatment was stable disease (SD) (n=2), partial response (PR) (n=8), or very good partial response (VGPR) (n=3). Median CD34+ cell dose was 3.24x106/kg (2.23-6.92x106). Median follow-up was 14.2 months (1-24.5). Median time to neutrophil engraftment was 12 d (11-15). One patient died before achieving platelet engraftment. For the remaining patients, median time to platelet engraftment was 16 d (12-20). Non-hematologic toxicities included grade 3 acute mucositis (n=1), lower GI complications (n=6), electrolyte disturbances (n=6), transaminase elevation (n=1) renal insufficiency (n=1), pulmonary edema (n=1), prolonged QTc (n=1), atrial fibrillation (n=1), and elevated troponin (n=1) and grade 4 acute sepsis (n=2), resulting in 1 death in cohort 2 on d +44. Seven patients went on to receive maintenance therapy: 3 with bortezomib, 3 with lenalidomide, and 1 with lenalidomide, dexamethasone, and C. Post-transplant disease status was assessed per protocol by SPEP, SPIF, and serum free light chains and light chain ratio. Nine patients were evaluable on d +100. One patient had SD, 6 had VGPR, and 2 had complete response (CR). Six out of 7 (86%) evaluable patients on d +365 remain disease progression-free.In summary, BCM conditioning prior to AHSCT at the doses described in cohort 3b seems feasible with manageable toxicities. Five additional patients are being enrolled at the same dose level. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Benefit of percutaneous endoscopic gastrostomy in patients undergoing definitive chemoradiotherapy for locally advanced nasopharyngeal carcinoma.

Background and aimTo evaluate the impact of percutaneous endoscopic gastrostomy (PEG) tube on nutritional status, treatment-related toxicity, and treatment tolerance in patients with locally advanced nasopharyngeal carcinoma (NPC) who underwent chemoradiotherapy.Patients and methodsWe enrolled 133 consecutive non-metastatic NPC (III/IV stage) patients, who were treated with prophylactic PEG feeding before the initiation of concurrent chemoradiotherapy (CCRT) between June 1, 2010 and June 30, 2014. Meanwhile, another 133 non-PEG patients, who were matched for age, gender, and tumor, node, metastases stage, were selected as historical control cohort. Weight and nutritional status changes from pre-radiotherapy to the end of radiotherapy were evaluated, and treatment tolerance and related acute toxicities were analyzed as well.ResultsWe found that significantly more patients (91.73%) in the PEG group could finish two cycles of CCRT, when compared with those in the non-PEG group (57.89%) (P<0.001). We also indicated that more patients (50.38%) in the non-PEG group experienced weight loss of ≥5%, while the phenomenon was only found in 36.09% patients in the PEG group (P=0.019). In addition, the percentage of patients who lost ≥10% of their weight was similar in these two groups. Changes in albumin and prealbumin levels during radiotherapy in the non-PEG group were higher than those obtained for the PEG group with significant differences (P-values of 0.023 and <0.001, respectively). Furthermore, patients in the PEG group had significantly lower incidence of grade III acute mucositis than those in the non-PEG group (22.56% vs 36.84%, P=0.011). Tube-related complications occurred only in 14 (10.53%) patients in the PEG group, including incision infection of various degrees.ConclusionPEG and intensive nutrition support may help to minimize body weight loss, maintain nutritional status, and offer better treatment tolerance for patients with locally advanced NPC who underwent CCRT.

Temporal Pattern of Acute Radiation Mucositis by Oral Mucosal Dose Surface Model in Head and Neck Cancers Treated by Carbon Ion Radiation Therapy

Temporal Pattern of Acute Radiation Mucositis by Oral Mucosal Dose Surface Model in Head and Neck Cancers Treated by Carbon Ion Radiation Therapy

Toward a model-based patient selection strategy for proton therapy: External validation of photon-derived normal tissue complication probability models in a head and neck proton therapy cohort

ObjectiveTo externally validate head and neck cancer (HNC) photon-derived normal tissue complication probability (NTCP) models in patients treated with proton beam therapy (PBT). MethodsThis prospective cohort consisted of HNC patients treated with PBT at a single institution. NTCP models were selected based on the availability of data for validation and evaluated by using the leave-one-out cross-validated area under the curve (AUC) for the receiver operating characteristics curve. Results192 patients were included. The most prevalent tumor site was oropharynx (n=86, 45%), followed by sinonasal (n=28), nasopharyngeal (n=27) or parotid (n=27) tumors. Apart from the prediction of acute mucositis (reduction of AUC of 0.17), the models overall performed well. The validation (PBT) AUC and the published AUC were respectively 0.90 versus 0.88 for feeding tube 6months PBT; 0.70 versus 0.80 for physician-rated dysphagia 6months after PBT; 0.70 versus 0.68 for dry mouth 6months after PBT; and 0.73 versus 0.85 for hypothyroidism 12months after PBT. ConclusionAlthough a drop in NTCP model performance was expected for PBT patients, the models showed robustness and remained valid. Further work is warranted, but these results support the validity of the model-based approach for selecting treatment for patients with HNC.

Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy

PurposeCurrent normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue—sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the dose data could overcome this limitation.Methods and MaterialsFDA was applied to modeling of severe acute mucositis and dysphagia resulting from head and neck RT. Functional partial least squares regression (FPLS) and functional principal component analysis were used for dimensionality reduction of the dose-volume histogram data. The reduced dose data were input into functional logistic regression models (functional partial least squares—logistic regression [FPLS-LR] and functional principal component—logistic regression [FPC-LR]) along with clinical data. This approach was compared with penalized logistic regression (PLR) in terms of predictive performance and the significance of treatment covariate—response associations, assessed using bootstrapping.ResultsThe area under the receiver operating characteristic curve for the PLR, FPC-LR, and FPLS-LR models was 0.65, 0.69, and 0.67, respectively, for mucositis (internal validation) and 0.81, 0.83, and 0.83, respectively, for dysphagia (external validation). The calibration slopes/intercepts for the PLR, FPC-LR, and FPLS-LR models were 1.6/−0.67, 0.45/0.47, and 0.40/0.49, respectively, for mucositis (internal validation) and 2.5/−0.96, 0.79/−0.04, and 0.79/0.00, respectively, for dysphagia (external validation). The bootstrapped odds ratios indicated significant associations between RT dose and severe toxicity in the mucositis and dysphagia FDA models. Cisplatin was significantly associated with severe dysphagia in the FDA models. None of the covariates was significantly associated with severe toxicity in the PLR models. Dose levels greater than approximately 1.0 Gy/fraction were most strongly associated with severe acute mucositis and dysphagia in the FDA models.ConclusionsFPLS and functional principal component analysis marginally improved predictive performance compared with PLR and provided robust dose-response associations. FDA is recommended for use in normal tissue complication probability modeling.

Normal tissue complication probability (NTCP) modelling using spatial dose metrics and machine learning methods for severe acute oral mucositis resulting from head and neck radiotherapy

Background and purposeSevere acute mucositis commonly results from head and neck (chemo)radiotherapy. A predictive model of mucositis could guide clinical decision-making and inform treatment planning. We aimed to generate such a model using spatial dose metrics and machine learning. Materials and methodsPredictive models of severe acute mucositis were generated using radiotherapy dose (dose–volume and spatial dose metrics) and clinical data. Penalised logistic regression, support vector classification and random forest classification (RFC) models were generated and compared. Internal validation was performed (with 100-iteration cross-validation), using multiple metrics, including area under the receiver operating characteristic curve (AUC) and calibration slope, to assess performance. Associations between covariates and severe mucositis were explored using the models. ResultsThe dose–volume-based models (standard) performed equally to those incorporating spatial information. Discrimination was similar between models, but the RFCstandard had the best calibration. The mean AUC and calibration slope for this model were 0.71 (s.d.=0.09) and 3.9 (s.d.=2.2), respectively. The volumes of oral cavity receiving intermediate and high doses were associated with severe mucositis. ConclusionsThe RFCstandard model performance is modest-to-good, but should be improved, and requires external validation. Reducing the volumes of oral cavity receiving intermediate and high doses may reduce mucositis incidence.

Efficacy and mucosal toxicity of concomitant chemo-radiotherapy in patients with locally-advanced squamous cell carcinoma of the head-and-neck in the light of a novel mathematical model.

In the last several decades, combined radiotherapy (RT) and chemotherapy (CT) have been recognized as feasible in locally-advanced-squamous-cell-carcinoma of the head-and-neck (LA-HNSCC). Several meta-analyses identified concurrent RT+CT (CRT) most likely effective approach respect to RT-alone. However, radiobiological models comparing different chemotherapeutic schedules against delivered RT fractionation schedule for overall survival and toxicity are still needed. Based on 9 randomized trials (2785 patients), radiobiological models and multivariate logistic regression model were used to derive dose-response curves and estimate the 5-year-overall survival (OS) and ≥G3 acute mucositis rate of CRT or RT-alone. Equivalent dose at 2 Gy/fraction (EQD2) was calculated using the linear quadratic model. The effect of CRT schedules, considering the CT type and its administration schedule and the HPV status of tumors were estimated using the univariate/multivariate logistic regression. The multivariate logistic regression model for 5y-OS indicated EQD2 and the type of CT, the chemo-sensitization fraction and the HPV status significant prognostic factors, while for toxicity both EQD2 and the concomitant administration of 5-fluorouracil (5Fu) resulted as significant prognostic factors. Combined schedules cisplatin (DDP)+/-5Fu+RT produced the higher OS compared with combined carboplatin+/-5Fu+RT or RT-alone. The concomitant administration of Fu and schedule with high EQD2 increase the rate of observed ≥G3 acute mucositis. Multivariate logistic regression models can be used to predict CRT effect in terms of OS and ≥G3-mucositis, contributing to the identification of novel treatment schedules.

Soft Tissue Necrosis in Head and Neck Cancer Patients After Transoral Robotic Surgery or Wide Excision With Primary Closure Followed by Radiation Therapy

Risk factors were evaluated for surgical bed soft tissue necrosis (STN) in head and neck cancer patients treated with postoperative radiation therapy (PORT) after transoral robotic surgery (TORS) or wide excision with primary closure. Sixty-seven patients were evaluated. STN was defined as ulceration and necrosis of the surgical bed or persistently unhealed high-grade acute mucositis with pain after PORT. The median RT dose of primary site was 63.6 Gy (range, 45–67.15 Gy) with 2 Gy/fx (range 1.8–2.2 Gy/fx). Total 41 patients (61.2%) were treated with concurrent chemoradiotherapy. The median follow-up period was 26 months. STN was diagnosed in 13 patients (19.4%). Most of the patients were treated with oral steroids, antibiotics, and analgesics and the lesions were eventually improved (median of 6 months after PORT). STN did not influence local control. A depth of invasion (DOI > 1.4 cm, odds ratio [OR] 14.04, p = 0.004) and maximum dose/fraction (CTVpmax/fx > 2.3 Gy, OR 6.344, p = 0.043) and grade 3 acute mucositis (OR 6.090, p = 0.054) were related to STN. The 12 (23.5%) of 51 oropharyngeal cancer patients presented STN, and the risk factors were DOI > 1.2 cm (OR 21.499, P = 0.005), CTVpmax/fx > 2.3 Gy (OR 12.972, P = 0.021) and grade 3 acute mucositis (OR 10.537, P = 0.052). Patients treated with TORS or WE with primary closure followed by PORT had a high risk of surgical bed STN. STN risk factors included DOI (>1.2–1.4 cm) and CTVpmax/fx (>2.3 Gy). Radiation therapy after TORS must be carefully designed to prevent STN.

C-Reactive Protein as a Biomarker of Radiation Therapy and Chemotherapy Toxicity Monitoring in Patients With Head and Neck Cancer

C-reactive protein (CRP) is a serum protein elevated in a variety of illnesses, including cancer. Also some data exist that CRP level is correlated with acute mucositis in patients (pts) with head and neck cancer (HNC) treated with radiation therapy (RT) and significantly elevated when dose/fraction number is increased. The purpose of this study is to show how CRP behaves before and after HNC RT with or without chemotherapy. From 2010 to 2015, 401 pts (318 men and 83 women) with a mean age of 58 years (range 20-81) with oral cavity (5), nasopharynx (30), oropharynx (133), hypopharynx (47), larynx (180), or unknown primary (6) cancer were under treatment. Tumor stage was evaluated in all pts: T0-6, T1-60, T2-147, T3-119, T4-69, and N0-174, N1-52, N2-143, and N3-32. Four schedules of treatment have been used: RT alone (RTA, 178 pts), concurrent chemoradiation therapy (CRC, 93 pts), and induction chemotherapy (IC) followed by RTA (46 pts) or CRC (84 pts). CRP (normal level, <2.87mg/L) was measured as follows: before IC (if applied) or before RTA/CRC, every week during RTA/CRC, and, finally, 1 month after treatment. Total number of CRP measurements was 3622. Initial CRP level was normal in 56% of pts; in 44% it was elevated (median 6.05 mg/L) but not correlated with tumor advancement. After IC, normalization of CRP was observed in 73% of pts (median CRP decreased from 3.12 to 1.24 mg/L). During RT progressive, week by week up to week 6, elevation of CRP was observed for RTA and CRC with no difference between both treatments. However, evident impacts of initial CRP level and IC were noted; in patients who had abnormal initial CRP and/or IC, significantly higher CRP levels were observed over RTA and CRC. There was no correlation observed between CRP and total dose or overall volume of radiated tissue. CRP may be a useful laboratory parameter in monitoring of toxicity in HNC patients undergoing RTA and CRC. IC leads to significant reduction/normalization of CRP in the majority of patients, which may reflect an anti-inflammatory effect in tumor burden. Similar CRP levels in patients treated with RTA and CRC may suggest that tumor and normal tissue radiation sensitivity is an essential proinflammatory factor.

PET/CT in CT Simulation: Significance of a Standardized Positioning Protocol for Head and Neck Radiation Therapy Planning

233; Table 1 Pre-RT 2 weeks 4 weeks 2 weeks post-RT Avg mucositis grade 0 1.33 2.67 1.67 FLT-PET SUVmax 10.5 3.25 1.55 2.15 FDG-PET SUVmax 8.53 5.53 4.27 5.13 Volume 94 Number 4 2016 Posters 923 mucositis in imaging interpretation, as FLT, unlike FDG, does not highlight metabolic or inflammatory activity of the tissue. A total of 9 PET scans were planned per patient (4 FLT-PET and 5 FDG-PET scans). Acute mucositis was recorded according to Common Terminology Criteria for Adverse Events version 4. PET scans were read by the same radiologist. Maximal standard uptake value of FDG-PET at each timepoint was compared with FLT-PET. Activity of both FLTand FDG-PET was also matched to the mucositis score to determine the correlation between PET activity and the severity of mucositis. Results: Three patients were enrolled in the first phase of the feasibility study. A total of 26 PET scans were obtained (missing was an FLT scan in 1 patient at week 2). All patients completed treatment according to the protocol. All patients developed mucositis, which nearly peaked at the end of week 4. Both FDG and FLT PET activity significantly decreased at week 2 and reached the lowest level at week 4. FDG-PET did not show activity in areas with the severe mucositis at and around the primary site, same as FLT-PET (see table). Interestingly, FLTas well as FDG-PET activity slightly increased at week 2 after RT at the mucosal sites while mocositis subsided to less than grade 2. At minimal follow-up of 1 year, all patients were without treatment failure. Conclusion: This study demonstrates that radiation-induced mucositis in oral cavity or oropharynx does not increase FDG or FLT uptake during radiation therapy. Author Disclosure: S. Song: None. J. Zweit: None. M.J. Fratkin: None. J.F. Williamson: None. D. Holdford: None.

Clinical Outcomes and Patterns of Disease Recurrence After Intensity Modulated Proton Therapy for Oropharyngeal Squamous Carcinoma

A single-institution prospective study was conducted to assess disease control and toxicity of proton therapy for patients with head and neck cancer. Disease control, toxicity, functional outcomes, and patterns of failure for the initial cohort of patients with oropharyngeal squamous carcinoma (OPC) treated with intensity modulated proton therapy (IMPT) were prospectively collected in 2 registry studies at a single institution. Locoregional failures were analyzed by using deformable image registration. Fifty patients with OPC treated from March 3, 2011, to July 2014 formed the cohort. Eighty-four percent were male, 50% had never smoked, 98% had stage III/IV disease, 64% received concurrent therapy, and 35% received induction chemotherapy. Forty-four of 45 tumors (98%) tested for p16 were positive. All patients received IMPT (multifield optimization to n=46; single-field optimization to n=4). No Common Terminology Criteria for Adverse Events grade 4 or 5 toxicities were observed. The most common grade 3 toxicities were acute mucositis in 58% of patients and late dysphagia in 12%. Eleven patients had a gastrostomy (feeding) tube placed during therapy, but none had a feeding tube at last follow-up. At a median follow-up time of 29 months, 5 patients had disease recurrence: local in 1, local and regional in 1, regional in 2, and distant in 1. The 2-year actuarial overall and progression-free survival rates were 94.5% and 88.6%. The oncologic, toxicity, and functional outcomes after IMPT for OPC are encouraging and provide the basis for ongoing and future clinical studies.

Evolution of radiation techniques in the treatment of mediastinal lymphoma: from 3D conformal radiotherapy (3DCRT) to intensity-modulated RT (IMRT) using helical tomotherapy (HT): a single-centre experience and review of the literature.

To evaluate radiation techniques and their toxicity in the treatment of Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL) with mediastinal disease over a 10-year period. Between 2003 and 2015, 173 patients with Stage I-III nodal lymphoma were treated in our institution: some of these patients were irradiated for HL or NHL with mediastinal disease. Some of the patients were treated by three-dimensional conformal radiotherapy (3DCRT), others by intensity-modulated radiotherapy (IMRT). We studied 26 males and 43 females with a median age of 26 years. The median follow-up was 43 months. 49 patients were treated by 3DCRT and 20 patients by IMRT. The median dose received by patients treated for NHL was 40 Gy (range: 36-44 Gy), and the median dose received by patients with HL was 30 Gy (range: 30-36 Gy). Between 2003 and 2006, 16 patients were treated by 3DCRT vs 0 patients by IMRT. Between 2007 and 2009, 16 patients received 3DCRT and one patient received IMRT. Between 2010 and 2015, 19 patients received IMRT, and no patients received 3DCRT. 11 of the 20 (55%) patients treated by IMRT and 35 of the 49 (71.4%) patients treated by 3DCRT experienced acute toxicity. Among the patients treated by 3DCRT, one patient experienced Grade 1 radiation pneumonitis and two patients experienced Grade 1 acute mucositis. No late toxicity was observed in patients treated by IMRT. Improvement of radiation techniques for HL and NHL appears to have improved acute and late clinical safety. Longer follow-up is necessary to evaluate very late toxicity. Improvement of radiation techniques for HL and NHL appears to improve the tolerance.

High-dose-rate interstitial brachytherapy in early stage oral tongue cancer - 15 year experience from a tertiary care institute.

PurposeTo determine outcomes of interstitial high-dose-rate brachytherapy (HDR-BT) in patients with early stage oral tongue cancer.Material and methodsNinety-two patients with stage I and II oral tongue cancer were treated with HDR-BT between 1999 and 2014: brachytherapy alone = 62 (67.4%), and combination of external beam radiotherapy (EBRT) and brachytherapy = 30 (32.6%). Median follow-up was 53.5 months. Patterns of failure, overall survival (OS), disease-free survival (DFS), local control rates (LCR), and nodal control rates (NCR) were determined.Results5-year OS, DFS, LCR, and NCR were 73.2%, 58.2%, 64.2%, and 83.8%, respectively. In total, 43 patients (46.7%) failed treatment: isolated local failures = 28 (30.4%), isolated nodal failures = 8 (8.7%), both local and regional failures = 7 (7.6%). While in T1 stage, 5 year LCR were significantly higher in brachytherapy alone group compared to combined EBRT and brachytherapy group (81.7% vs. 62.5%, p = 0.04), the isolated nodal failure rates were not significantly different among the two groups. For T2 stage, NCR were higher in combined EBRT and brachytherapy group compared to brachytherapy alone (92.9% vs. 74.3%). Acute mucositis (grade ≥ 2) was seen more in brachytherapy alone group compared to the combined modality group (87% vs. 66%), and this correlated significantly with the higher biological equivalent dose (BED) in the brachytherapy alone group.ConclusionsOur study recommends treating patients with brachytherapy alone in T1 stage, and demonstrates the need for addressing nodal region either by neck dissection or nodal irradiation in T2 stage patients. Also, the study highlights the need for dose escalation (from the doses used in the study) in both T1 and T2 stage tumors when using interstitial brachytherapy either as sole modality or as a boost.

Results of 2 dimensional postoperative radiotherapy treatment in carcinoma buccal mucosa patients: A regional cancer centre experience

Purpose/Objective(s): In India > 1 million new cases of cancer diagnosed every year. 40-50% of these cases are of head and neck cancer because of tobacco overuse. In our institute we have almost 1000-1300 new cases of Carcinoma Buccal Mucosa reported every year. From which 70-75% are surgically operable. For post-operative Radiotherapy treatment, we treat most of our patients by 2 Dimensional conventional treatments. Purpose of this study is to assess toxicity & long term results of postoperative carcinoma buccal mucosa cases treated by 2 Dimensional conventional treatment planning. Materials/Methods: From January 2009 to January 2012, almost 1980 postoperative cases of Carcinoma Buccal mucosa were referred for radiotherapy treatment. From which 1584 cases were suitable for postoperative 2 Dimensional Conventional planning. In selected cases, 71%, 18%, 11% cases were of Stage IV, III, II (close margin) respectively. Postoperative chemotherapy and radiotherapy was indicated in 475 patients. For all patients Plaster of Paris cast was prepared & X-ray was taken on Simulator machine. Target volume was drawn on x-ray & treatment plan generated on contour drawn with 90-95% isodose line covering the target, with hot spot of +10% on 2D Plato treatment planning system. All patients were treated with unilateral Anterior Posterior Lateral wedge pair technique for buccal mucosa and unilateral lower neck was given in indicated patients. Dose prescribed was 60 Gy/30#, 2Gy/#, 5 days a week, total 6 weeks treatment. Treatment plan verified on day 2 and treatment started. In patients where postoperative chemotherapy and radiotherapy was used, chemotherapy was given Cisplatin 30mg/m[2] every weekly for 6 weeks. In most of the patients, treatment break was not required. All patients completed treatment successfully. Patients were assessed for locoregional control, acute & late toxicity and followed up for 3 years for disease free survival and overall survival. Results: Grade II & III acute mucositis was 82% & 18% respectively in 1109 patients who received only postoperative radiotherapy. For patients who received postoperative radiotherapy and chemotherapy Grade II and Grade III acute mucositis was seen in 75% & 25% respectively and side effects related to Cisplatin were managed conservatively. Almost all patients had Grade II skin reactions. Grade III skin reactions were observed in 8% of patients on post operative radiotherapy alone and 19% of patients on postoperative radiotherapy and chemotherapy but were manageable. All patients tolerated treatment well. For 1584 patients, follow up dropout rate was 20%. None of the patients developed significant late toxicity. As opposite parotid spared, no late complication of xerostomia observed. For 1268 patients, 1-, 2-, 3- year locoregional control rates were 82%, 75%, 68% respectively. Disease free survival rate was 63% (799 patients) & overall survival was almost 55% (697 patients) at median follow up for 40 months. Conclusion: 2D Conventional Radiotherapy Treatment Planning in our set up has shown very good results with almost 50% survival rates. It is less toxic treatment with fewer complications & less time consuming. It is highly cost effective treatment approach & results are very much encouraging.

Evaluation of efficacy of Caphosol in prevention and alleviation of acute side effects in patients treated with radiotherapy for head and neck cancers.

Aim of the studyOral mucositis is a common side effect of the oral mucosa due to anticancer therapy, especially for head and neck cancer. Caphosol is indicated for dryness of the mouth and oropharynx and treatment of mucositis due to irradiation or high-dose chemotherapy. The aim of the study was to evaluate the efficacy of Caphosol in preventing and alleviating mucositis due to radiotherapy in the head and neck region.Material and methodsCaphosol was used from the beginning of the irradiation and for two weeks more after the treatment was completed. Mucositis, xerostomia, and dysphagia were scored by radiotherapists. Subjective evaluation was made by patients. Caphosol was assessed in a non-blinded, matched clinical study. Each treatment arm consisted of 50 patients. The groups were similar. The only difference in the management protocol between the treatment arms was the use of Caphosol in the experimental arm.ResultsA statistically significant difference in mean severity of early irradiation-induced side effects between the studied groups was observed with respect to: mucositis in the clinical target volume (CTV) area, mucositis in the increased dose (boost) area, dysphagia and xerostomia (p < 0.001 for all reactions). In the group of patients who used Caphosol, the mucositis was less intense, both in the CTV and in the boost area.ConclusionsThe use of Caphosol reduces the severity of acute mucositis, dysphagia and xerostomia, exerting a positive effect on comfort in the oral cavity in patients irradiated for head and neck tumors.

Factors Influencing Compliance to Radical Treatment of Middle Thoracic Esophageal Cancer: An Audit from a Regional Cancer Centre.

Background:The aim of this study is to identify the factors responsible for interruption of planned treatment in patients of carcinoma mid-thoracic esophagus and also discuss the strategies for improving treatment completion rates.Materials and Methods:Patients with nonmetastatic mid-thoracic esophageal cancer who received treatment by multimodality approach using chemotherapy, radiation, and/or surgery were retrospectively analyzed. Factors influencing compliance with planned treatment completion were evaluated, and their significance was determined using multivariate Cox regression analysis.Results:Ninety-one patients were reviewed. Median follow-up period was 11 months. Of 15 patients planned with neoadjuvant chemoradiation followed by surgery (Group 1), only 6 (40%) could complete the treatment. Similarly, only 19 out of 36 patients (52.8%) completed the planned definitive chemoradiation (Group 2). Furthermore, of forty patients planned with definitive radiotherapy (Group 3), 29 patients only (72.5%) completed this schedule. The rate of completion of therapy was worst in Group 1. The most common reason for noncompletion of planned treatment was nutritional inadequacy and excessive weight loss in all groups. In addition, chemotherapy-induced myelosuppression (P = 0.05) was the factor leading to treatment interruption in Group 2 and radiation-induced acute mucositis (P = 0.02) and lost to follow-up (P = 0.02) were the factors in Group 3.Conclusions:Rate of treatment completion significantly impacts survival rates. Nutritional inadequacy was the most common factor for noncompletion of planned treatment. A well-trained management team consisting of oncologist, dietitian, and psychotherapist can help overcome these factors and thereby improve the treatment completion rates.

Gemcitabine-Based Chemoradiation in the Treatment of Locally Advanced Head and Neck Cancer: Systematic Review of Literature and Meta-Analysis.

Platinum-based concurrent chemoradiation (CCRT) improves locoregional control and overall survival of locoregionally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) when compared to radiotherapy alone, but this approach is hampered by significant toxicity. Therefore, alternative ways to enhance the radiation effects are worth investigating. Gemcitabine (2',2'-difluorodeoxycytidine), in addition to its activity against a variety of solid tumors, including SCCHN, is one of the most potent radiosensitizers, and it has an overall favorable safety profile. In this paper, the clinical experience with gemcitabine-based chemoradiation in the treatment of patients with LA-SCCHN is reviewed. We conducted a review of the literature on the clinical experience with radiotherapy combined with either single-agent gemcitabine or gemcitabine/cisplatin-based polychemotherapy for the treatment of patients with LA-SCCHN. We also searched abstracts in databases of major international oncology meetings from the last 20 years. A meta-analysis was performed to calculate pooled proportions with 95% confidence intervals (CIs) for complete response rate and grade 3-4 acute mucositis rate. A total of 13 papers were eligible for the literature review. For schedules using a gemcitabine dose intensity (DI) below 50 mg/m(2) per week, the complete response rate was 86% (95% CI, 74%-93%) with grade 3-4 acute mucositis rate of 38% (95% CI, 27%-50%) and acceptable late toxicity. In one of the studies employing such low DIs, survival data were provided showing a 3-year overall survival of 50%. Compared with DI ≥50 mg/m(2) per week, there was no difference in the complete response rate (71%; 95% CI, 55%-83%; p = .087) but a significantly higher (p < .001) grade 3-4 acute mucositis rate of 74% (95% CI, 62%-83%), often leading to treatment interruptions (survival data provided in 8 studies; 3-year overall survival, 27%-63%). Late toxicity comprising mainly dysphagia was generally underreported, whereas information about xerostomia and skin fibrosis was scarce. This review highlights the radiosensitizing potential of gemcitabine and suggests that even very low dosages (less than 50 mg/m(2) per week) provide a sufficient therapeutic ratio and therefore should be further investigated. Refinements in radiation schemes, including intensity-modulated radiation therapy, in combination with low-dose gemcitabine and targeted agents, such as cetuximab, are currently being investigated. Cisplatin-based concurrent chemoradiation (CCRT) has become the standard treatment of locally advanced head and neck cancer (LAHNC). This approach is hampered by significant toxicity. This paper reviews the studies using gemcitabine as an alternative radio-sensitizer for CCRT in patients with LAHNC. In this capacity, despite its mild intrinsic toxicity, gemcitabine comes with high rates of severe mucositis when used in dosages exceeding 50 mg/m(2) per week. CCRT with low-dose gemcitabine provides a sufficient therapeutic ratio, combining clinical activity, similar to the higher-dose regimens, with lower toxicity. Further investigation is warranted.

Double-Blind Randomized Phase 3 Study Comparing a Mixture of Natural Ingredients Versus Placebo in the Prevention of Acute Mucositis During Chemoradiation Therapy for Head and Neck Cancer

Double-Blind Randomized Phase 3 Study Comparing a Mixture of Natural Ingredients Versus Placebo in the Prevention of Acute Mucositis During Chemoradiation Therapy for Head and Neck Cancer