Acute Mucosal Reactions Research Articles

Review: Food-induced mucosal alterations visualized using endomicroscopy.

Confocal laser endomicroscopy (CLE) is a novel technique allowing real time invivo microscopy during standard endoscopy. Recently, acute mucosal alterations after food administration visualized by CLE have been linked to symptoms in irritable bowel syndrome (IBS). Interestingly, the observed reactions occurred in subjects without demonstrable allergic sensitization to food-this is in line with mechanistic research showing local but not systemic allergic sensitization to foods in an animal model for IBS. Here, European experts conducting CLE with food administration provide a narrative review of the available literature and propose practical guidance on the use of this technique. CLE allows physicians to observe acute mucosal reactions after the application of food to the duodenal mucosa in patients with functional gastrointestinal disorders. Some open-label interventions show a symptomatic benefit when patients exclude the nutrient that triggered an acute mucosal reaction. However, many technical, mechanistic, and clinical questions remain unanswered to date. Technically, the interobserver variability and learning curve requires systematic evaluation and criteria or cutoffs for alterations require validation. Mechanistic studies are needed to enhance our understanding of the mechanisms underlying observed alterations. Finally, rigorous blinded controlled studies are needed to assess a link of these observed alterations with symptom generation. CLE offers a platform allowing scientific insights related to food induced acute mucosal alterations. However, many questions remain unanswered, and more research is warranted to understand the role of acute mucosal alterations visualized upon food administration in IBS pathophysiology and treatment.

A Comparative Study of Two Split Course Accelerated Hypo-fractionated Radiation Therapy (SCAHRT) Schedules in Locally Advanced Head and Neck Carcinoma

Introduction: Head and neck cancers include malignant neoplasms that develop in the oral cavity, nasal cavity, paranasal sinuses, pharynx, larynx and salivary glands. Out of the newly diagnosed patients of head and neck carcinoma in India, most of the patients present in locally advanced stage. Because of extensive local disease and associated co-morbidities and compromised KPS, palliative radiation therapy is preferred treatment for these patients. Material and methods: The study was conducted on 60 previously untreated, histo-pathologically proven patients of locally advanced head and neck cancer who were randomized in two equal groups by draw of lots. Study group received radiation dose of 30 Gy/ 10 fractions / 2 weeks followed by repeat dose of 30 Gy/ 10 fractions / 2 weeks (Total dose 60 Gy in 20 fractions delivered with a gap of 4 weeks). Control group received radiation dose of 20 Gy/ 5 fractions/ 5 days followed by repeat dose of 20 Gy/ 5 fractions/ 5 days followed by repeat dose of 20 Gy/ 5 fractions/ 5 days (Total dose 60 Gy in 3 sessions with a gap of 3 weeks each). Objectives were to compare efficacy of above schedules based on symptomatic relief and overall tumor response and to compare the toxicities of the above schedules. Results and Conclusion: To expedite the treatment time in tertiary care centres, control group (20 Gy / 5 fractions / 1 week; 3 weekly X 3) was better than the study group (30 Gy / 10 fractions / 2 weeks; 4 weekly X 2) as it had comparable local control and toxicity (acute mucosal reactions being slightly higher in the study group) with the added advantage of only 15 total fractions (machine days) in control group rather than 20 total fractions (machine days) in study group. This reduced the patient visits to the hospital by one week (i.e. 5 fractions) with comparable local control and toxicity.

Complications of radio- and radiochemotherapy in patients undergoing major salivary gland cancer surgery.

The aim of this retrospective study was to present the prevalence of early and late radiation-induced reaction and factors affecting its formation and severity in patients after adjuvant radio- or radiochemotherapy in salivary gland cancer. A total of 113 patients with early and 91 with late radiation-induced reaction, irradiated in 2006-2016 were enrolled in the study. The frequency of acute mucosal radiation-induced reaction, time of onset, intensity, healing time, as well as the incidence of late radiation-induced reaction from the skin and subcutaneous tissue were analyzed. Factors that could influence the development and intensity of reaction were identified. Acute severity and the presence of late radiation-induced reaction do not affect overall survival. Dosage in the tumor bed site, as well as the dosage in the nodal region, affect the severity of the acute radiation-induced mucosal reaction. The severity of the early radiation-induced reaction is higher in men, more advanced patients (higher T and N+ in TNM classification), irradiated into a larger area, and those in whom two-dimensional planning and complementary chemoradiotherapy were applied. The late reaction of the skin and subcutaneous tissue was dominated by patients irradiated in the nodal regions and those with a higher intensity of early radiation-induced reaction. Supplementary radiotherapy or radiochemotherapy in salivary gland cancer is associated with acceptable toxicity which has no effect on overall survival.

Factors associated with acute oral mucosal reaction induced by radiotherapy in head and neck squamous cell carcinoma: A retrospective single-center experience.

To investigate risk factors for acute oral mucosal reaction during head and neck squamous cell carcinoma radiotherapy.A retrospective study of patients with head and neck squamous cell carcinoma who underwent radiotherapy from November 2013 to May 2016 in Anhui Provincial Cancer Hospital was conducted. Data on the occurrence and severity of acute oral mucositis were extracted from clinical records. Based on the Radiation Therapy Oncology Group (RTOG) grading of acute radiation mucosal injury, the patients were assigned into acute reaction (grades 2–4) and minimum reaction (grades 0–1) groups. Preradiotherapy characteristics and treatment factors were compared between the 2 groups. Multivariate logistic regression analysis was used to detect the independent factors associated with acute oral mucosal reactions.Eighty patients completed radiotherapy during the study period. Oral mucosal reactions were recorded as 25, 31, and 24 cases of grades 1, 2, and 3 injuries, respectively. Significant differences between acute reaction and minimum reaction groups were detected in cancer lymph node (N) staging, smoking and diabetes history, pretreatment platelet count and T-Helper/T-Suppressor lymphocyte (Th/Ts) ratio, concurrent chemotherapy, and total and single irradiation doses.Multivariate analysis showed that N stage, smoking history, single dose parapharyngeal irradiation, and pretreatment platelet count were independent risk factors for acute radiation induced oral mucosal reaction. Smoking history, higher grading of N stage, higher single dose irradiation, and lower preirradiation platelet count may increase the risk and severity of acute radiation oral mucosal reaction in radiotherapy of head and neck cancer patients.

Comparative Evaluation of Three Palliative Radiotherapy Schedules in Locally Advanced Head and Neck Cancer.

BackgroundThe aim of the study was to evaluate and compare the efficacy, tolerability and toxicity of three palliative radiotherapy (RT) schedules in locally advanced head and neck carcinoma (LAHNC), i.e. Quad Shot schedule, Christie schedule and conventional palliative schedule.MethodsThe patients were randomly divided into three groups of 30 each. Group I patients were planned for 14.8 Gy in 4 fractions over 2 days, repeated three weekly for two more cycles. Group II patients were planned for 50 Gy in 16 fractions over 3.1 weeks. Group III patients were planned for 20 Gy in 5 fractions over 5 days, repeated after an interval of 3 weeks. The quality of life was assessed before and after RT using University of Washington Quality of Life questionnaire version 4.ResultsLocal control rates were 84%, 76%, and 76% for groups I, II and III, respectively. Disease status at 6-month follow-up was no evidence of disease (20%, 28%, and 16%), residual disease (72%, 48%, and 76%), and recurrent disease (8%, 24%, and 8%) in groups I, II and III, respectively. Grade III acute skin reactions were 28%, 44%, and 16% in groups I, II and III, respectively. Grade III acute mucosal reactions were 36%, 56%, and 24% in group I, II and III, respectively. Quality of life improved in all groups after RT.ConclusionQuad Shot schedule may be used in LAHNC with better local control and acceptable toxicity as compared to conventional palliative RT schedule in Indian setting.

Randomized clinical trial on 7-days-a-week post-operative radiotherapy vs concurrent post-operative radiochemotherapy in locally advanced cancer of the oral cavity/oropharynx: a report on acute normal tissue reactions.

The purpose of the study was to evaluate acute normal tissue reactions and treatment compliance in a randomized clinical trial on 7-days-a-week post-operative radiotherapy (p-CAIR) vs post-operative concurrent radiochemotherapy (p-RTCT) in locally advanced cancer of the oral cavity/oropharynx. The sample analyzed at present represents approximately 30% of the intended future trial size. The patients were randomly assigned to receive 63 Gy in 1.8-Gy fractions 7 days a week (n = 44) or 63 Gy in 1.8-Gy fractions 5 days a week with concurrent cisplatin 80-100 mg per square metre of body surface area on Days 1, 22 and 43 of the course of radiotherapy (n = 40). Acute mucosal reactions were scored using the modified Dische system. 15 (17.9%) patients, including 5 patients in p-CAIR and 10 patients in p-RTCT, did not comply with the assigned radiation treatment, mostly because of rapid tumour progression or deteriorating general performance. In p-RTCT, 22 (55%) patients received less than the intended three courses of chemotherapy mostly owing to haematological toxicity. The average maximum mucosal severity score was 14.2 in p-CAIR compared with 13.4 in p-RTCT; the difference was not statistically significant (p = 0.31). The schedules compared (p-CAIR and p-RTCT) did not differ considerably with respect to acute mucosal reactions. Haematological toxicity in p-RTCT was elevated compared with p-CAIR. Both schedules were considered tolerable with respect to acute toxicity, which justifies further recruitment to the trial. The results show that early mucosal reactions are comparable in both trial arms but haematological toxicity is more pronounced during radiochemotherapy.

A Prospective Randomized Study Evaluating the Role of Oral Curcumin along with Chemoradiationin Management of Locally Advanced Head and Neck Carcinoma

Aim: This study was to evaluate the role of Curcumin along with or without chemoradiation in the management of locally advanced head and neck cancers (LHNC) in terms of tolerability, toxicity and response. Sixty treatment naive histopathologically proved cases LHNC were included in this prospective randomized study. Materials and Methods: Patients were randomly assigned to receive radical external beam radiotherapy (EBRT) with weekly cisplatin and capsule Curcumin from the first day of EBRT till the Original Research Article Kumar et al.; IJTDH, 16(1): 1-7, 2016; Article no.IJTDH.25780 2 completion in the dose of 1gm every 8 hourly (Group I/Study Group) and EBRT with weekly cisplatin only (Group II/Control Group). Results: There were lower grades of statistically insignificant haemoglobin (grade 2 p value0.300) and total leucocyte count (grade 1 p value0.313), toxicities in group II in compared to group I during treatment. The acute skin and mucosal reactions were less in group I than group II without any statistically significant association during treatment and follow ups. Statistically significant less blood urea (grade 1 p value0.019) toxicities observed in group I, in compared to group II during treatment. There were statistically significant fewer grade 3 and 4 vomiting (p value0.037) in group II. At one year follow up 67% was disease free in group I in comparison to 56% in group II. Conclusion: Curcumin, in management of LHNC, seems to decreases haematological, renal, skin and mucosal chemoradiation induced toxicities results in timely completion of intended treatment without any financial burden on patients and improves the disease control.

Smoking during radiotherapy for head and neck cancer and acute mucosal reaction

AimWe compared the incidence of RTOG/EORTC grade III and higher acute mucositis in patients with head and neck cancer who continued to smoke during radiotherapy with those who quit smoking. BackgroundThere are conflicting data on the relationship between smoking during radiotherapy and the severity of acute mucosal reaction. More studies dealing with this issue are needed. Materials and methodsAmong 136 patients receiving curative radio(chemo)therapy, 37 (27%) declared that they had not quit smoking during radiotherapy. The intensity of mucositis was scored daily by a nurse and weekly by a physician using the RTOG/EORTC scale. The main end-point of the study was the highest observed RTOG/EORTC grade of mucositis. ResultsPatients who smoked during radiotherapy (smokers) were younger than their counterparts who quit smoking (non-smokers), p=0.06. There were no other differences in the baseline characteristics between smokers and non-smokers. Grade III/IV acute mucositis was observed in 43.5% of all patients. The percentage of patients with grade III/IV acute mucositis was similar in smokers and non-smokers (46% vs. 42%, p=0.71). Nine patients (smokers [13.5%]; non-smokers [4%], p=0.05) required prolonged hospitalization to heal mucositis. ConclusionsIn the whole group, smoking during radiotherapy was not related to acute mucosal toxicity evaluated as the rate of the highest observed grade of mucositis.

Acute Mucosal Reactions in Conventional and Concomitant Boost Radiotherapy Schedules in Locally Advanced Oropharayngeal Carcinoma

Acute Mucosal Reactions in Conventional and Concomitant Boost Radiotherapy Schedules in Locally Advanced Oropharayngeal Carcinoma

Usefulness of Induction Chemotherapy Followed by Chemoradiation in the Treatment of Oropharyngeal Carcinoma

Usefulness of Induction Chemotherapy Followed by Chemoradiation in the Treatment of Oropharyngeal Carcinoma

Radiation Therapy-Related Changes in Serum Proteome Patterns Are Affected by Medium Doses of Radiation Delivered to Large Volumes of Normal Tissue

Intensity-modulated radiation therapy (IMRT) involves irradiation of increased volume of normal tissue with low and medium doses, which biological relevance is not clear yet. In current work the association of early biological effects of RT with dose and volume of irradiated tissue was analyzed. Serum proteome features were used as a surrogate for general reaction of whole patient's organism while acute mucosal reaction reflected local effect of irradiation.

The efficacy of oral Kangfuxin liquid combined with aerosolized inhalation of the liquid in prevention of acute radiation stomatitis

Objective To compare the efficacy of oral Kangfuxin liquid with that of aerosolized inhalation of the liquid in the prevention of acute radiation stomatitis in patients with head and neck tumors undergoing radiation therapy.Methods 200 patients with head and neck cancer were randomly divided into group A (oral group,100 patients) and group B (inhalation group,100 patients).Group A received oral Kangfuxin liquid 3 times daily,while group B received aerosolized inhalation of the liquid twice daily.The treatment lasted during the whole radiotherapy.Results The incidence rate of grades 2 to 3 radiation stomatitis was lower in group A than in group B (19％ in group A and 33％ in group B,x2=5.09,P＜0.05); there was a significant difference between the two groups.Conclusions Both oral Kangfuxin liquid and aerosolized inhalation of the liquid can reduce the severity of acute oral mucosal radiation reaction and shorten the duration of therapy.Oral Kangfuxin is better than inhalation.Combination therapy is more effective and is worth popularizing clinically. Key words: Kangfuxin liquid; Oral; Aerosolized inhalation; Acute radiation stomatitis, Radiation therapy; Efficacy

Acute mucosal reactions in patients with head and neck cancer

To investigate the individual pattern of acute mucosal radiation reactions (AMRR) in patients with head and neck cancer who were treated with radiotherapy alone. Reactions were evaluated daily on an individual basis according to the Dische scoring system. Treatment of 87 head and neck cancer patients comprised either conventional fractionation- (CF; n = 33), accelerated fractionation (AF; n = 33), hyperfractionated- (HPEFX; n = 12) or hypofractionated (HPOFX; n = 9) radiotherapy with radical intent. Daily evaluation of AMRR progression was performed prospectively using a modified, morphologically functional Dische scoring system. The daily sums of the score parameters were subsequently used to construct an individual AMRR course curve for each patient. A latency period ranging from 3 to 14 days between the start of radiotherapy and the occurrence of the first AMRR symptom was observed in all patients. Based on the three different shapes of AMRR course curve observed during radiotherapy, three types of AMRR course can be described: (1) a continual increase in AMRR intensity until the completion of radiotherapy; (2) the incidence of a plateau phase following the increase in AMRR (increase-plateau course) and (3) decreasing AMRR intensity with a healing phase. A continual increase in AMRR intensity was observed in about 25 % of CF and AF patients and in more than 50 % of HPOFX treatments. This type of reaction was not observed in the HPEFX group. The increase-plateau course was noted in the majority of AF and CF patients; in almost half of those treated with HPOFX and in all HPEFX patients. A decreasing AMRR intensity course was observed in 23 % of all patients, although not observed at all in the HPEFX and HPOFX fractionation groups. The course of AMRR during radiotherapy can differ between individual patients. After the initial increase in AMRR intensity, a stabilization of the reaction--visible as a plateau phase on the course curve--is observed in the majority of patients. A proportion of the irradiated patients experience a continual increase in AMRR intensity up until the end of radiotherapy. A further group of patients exists in whom signs of AMRR healing are observed during the final stages of radiotherapy.

Acute mucosal radiation reactions in patients with head and neck cancer

The goal of this research was to evaluate the healing processes of acute mucosal radiation reactions (AMRR) in patients with head and neck cancer. In 46patients with oral and oropharyngeal cancer patients irradiated with conventional (n = 25) and accelerated (n = 21) dose fractionation AMRR was evaluated daily during and after radiotherapy. Complex of morphological and functional symptoms according to the Dische score were collected daily until complete healing. Duration of healing after the end of radiotherapy ranged widely (12-70days). It was on the average 8days longer for accelerated than for conventional radiotherapy (p = 0.016). Duration of dysphagia was also longer for accelerated irradiation (11days, p = 0.027). Three types of morphological symptoms were observed as the last symptom at the end of AMRR healing: spotted and confluent mucositis, erythema, and edema. Only a slight correlation between healing duration and area of irradiation fields (r = 0.23) was noted. In patients with confluent mucositis, two morphological forms of mucosal healing were observed, i.e., marginal and spotted. The spotted form was noted in 71% of patients undergoing conventional radiotherapy and in 38% of patients undergoing accelerated radiotherapy. The symptoms of mucosal healing were observed in 40% patients during radiotherapy. The wide range of AMRR healing reflects individual potential of mucosa recovery with longer duration for accelerated radiotherapy. Two morphological forms of confluent mucositis healing were present: marginal and spotted. Healing of AMRR during radiotherapy can be observed in a significant proportion of patients.

Results of carbon ion radiotherapy for head and neck cancer

PurposeTo evaluate the efficacy of carbon ion radiotherapy for head-and-neck cancer in a phase II clinical trial. Materials and methodsBetween April 1997 and February 2006, 236 patients with locally advanced, histologically proven, and new or recurrent cancer of the head and neck were treated with carbon ions. The treatment dose was 64.0GyE/16 fractions/4weeks (or 57.6GyE/16 fractions/4weeks when the wide-range skin was included in the target volume). ResultsThere were grade 3 acute skin reactions in 6% and grade 3 acute mucosal reactions in 10% with no acute reactions worse than grade 3, and grade 2 late skin reactions in 3% and grade 2 late mucosal reactions in 2% with no late reactions worse than grade 2. The 5-year local control rate, by histological type, was 75% for the 85 patients with malignant melanoma, 73% for the 69 with adenoid cystic carcinoma, 73% for the 27 with adenocarcinoma, 61% for the 13 with papillary adenocarcinoma, 61% for the 12 with squamous cell carcinoma and 24% for the 14 with sarcomas. The 5-year over-all survival rate was 68% for adenoid cystic carcinoma, 56% for adenocarcinoma and 35% for malignant melanoma. ConclusionsCarbon ion radiotherapy for head and neck cancer showed the therapeutic effectiveness for malignant melanoma and adenoid cystic carcinoma without severe morbidity of the normal tissues.

Postoperative Continuous 7-days-a-week Radiotherapy for High-risk Squamous Cell Cancer of the Head and Neck: Long-term Results of a Randomized Clinical Trial

To present long-term results of a randomized clinical trial on postoperative continuous 7-days-a-week radiotherapy in high-risk squamous cancer of the head and neck. Between 2001 and 2004, 279 patients with high-risk squamous cell cancer of the larynx (158 patients.) or cancer of the oral cavity/oropharynx (121 patients.) were enrolled. They were stratified according to the primary cancer site (larynx vs. others) and the treating center (Gliwice vs. Bydgoszcz) and randomized to receive 63 Gy in fractions of 1.8 Gy given 5-days-a-week (140 patients: p-CF) or 7-days-a-week (139 patients: p-CAIR). The analysis of loco-regional tumor control was a primary endpoint of the trial. Survival curves were compared using log-rank test. Hazard rates were estimated using Cox regression model. Two hundred seventy-five patients were eligible for the analysis (98.9%). Acute mucosal reactions were more severe in p-CAIR as compared to p-CF, and this transformed into higher peak incidence of Grade >1 subcutaneous fibrosis (38% vs. 27%), bone necrosis (9% vs. 2%) and xerostomia (43% vs. 28%). Some of these reactions subsided, however, with time. Seven-year loco-regional tumor control was 60.9% in p-CF vs. 65.7% in p-CAIR, the difference did not appear statistically significant (p = 0.67, RR = 0.92, 95% CI, 0.60-1.39). There were also no significant differences in 7-year metastases-free survival (88.3% vs. 84.9%) and second cancer-free survival (82.7% vs. 85.5%) for p-CF vs. p-CAIR, respectively. A trend toward improvement from p-CAIR was apparent for 7-year local control (68.7% in p-CF vs. 79.8% in p-CAIR, p = 0.28, RR = 0.76) as opposed to nodal control (79.5% in p-CF vs. 81.1% in p-CAIR, p = 0.95, RR = 0.98). Also, there was a strong trend toward improvement in 7-year LRC from p-CAIR among the patients with cancer of the oral cavity/oropharynx (51.8% vs. 67.7%, p = 0.10, RR = 0.60) as opposed to the patients with cancer of the larynx (67.0% vs. 64.3, p = 0.34, RR = 1.33). Seven-year overall survival did not significantly differ between the groups (30.6% p-CF vs. 35.7 p-CAIR, p = 0.56, RR = 0.91, 95% CI 0.68-1.23). A crude rate of distant metastases and second cancer was 18.5% (51/275) becoming, thus, a competitive cause of treatment failure as compared to loco-regional recurrences (89/275 = 32.4%). This study did not show significant improvement in LRC from shortening the overall radiation treatment time in a group of patients treated with postoperative radiotherapy for high-risk squamous-cell cancer of the head and neck. A trend toward such improvement was, however, noticeable in a subset of patients with cancer of the oral cavity/oropharynx.

Final results: A phase I study of sorafenib and palliative radiation in patients with malignancy in the thorax, abdomen, or pelvis.

e13602 Background: The combination of VEGF-directed therapy with radiotherapy (RT) has shown preclinical promise but data of potential toxicities are limited. We initiated a phase I study combining sorafenib (S) with palliative radiotherapy in patients with primary or metastatic malignancy in the thorax, abdomen or pelvis. Methods: Cohorts of 3-6 patients with measureable tumor lesions in the chest, abdomen or pelvis were treated with S (dose levels: 1 - 200 od; 2 - 200 mg bid; 3 - 400 mg bid) for 4 weeks and RT (30 Gy in 10 daily fractions) in weeks 2 and 3. Each anatomic cohort escalated S dose independently. Primary endpoint: maximum tolerated dose of S (MTD) - the dose level below that resulting in ≥ 2/6 patients with dose limiting, acute, in-field toxicities (≥Gr 3 and attributable to RT). Results: From May 2007 to Nov 2010, 34 patients were entered on study (thorax/abdomen/pelvis - 14/16/4). The thoracic, abdominal and pelvic cohorts reached dose levels 3, 3 and 1, respectively. Significant S dose modifications occurred in 6/10 patients on dose level 3 due to S systemic toxicities. DLTs were noted in each cohort: thorax dose level 2 – Gr 3 esophagitis; abdomen dose level 3: Gr 3 ALT elevation; pelvis dose level 1 – Gr 5 perforation of tumor-involved bowel. No other high grade, RT-related toxicities were observed. Grade 2 acute RT skin toxicity was observed in 7/8 patients who completed both 4 weeks of S on dose level 2 or 3, and had RT plans using only 2 or 3 beams implying a minimum drug/RT dose threshold for this phenomenon. Conclusions: MTD was not defined for any anatomic cohort. The trial was terminated as systemic toxicity of sorafenib resulted in dose reductions and discontinuations at 400 mg bid precluding efficient evaluation of RT-related toxicity combined with this dose of sorafenib. Gr 2 RT dermatitis was consistently seen in patients receiving 4 weeks of uninterrupted sorafenib 200 or 400 mg bid. The severity and prevalence of Gr 2 dermatitis was greater than expected for 30 Gy in 10 fraction RT. One patient developed Gr 3 esophagitis following esophageal RT. It is likely that sorafenib in conjunction with higher dose RT may require drug dose or schedule modification to mitigate acute cutaneous or mucosal reactions.

Association between plasma proteome profiles analysed by mass spectrometry, a lymphocyte-based DNA-break repair assay and radiotherapy-induced acute mucosal reaction in head and neck cancer patients

Purpose: The plasma proteome was analysed as a potential source of markers of radiosensitivity in patients treated with definitive radiotherapy for head and neck cancer.Materials and methods: Acute mucosal reactions that developed during radiotherapy were assessed in 55 patients. Blood samples were collected from each patient before the treatment and also from 50 healthy donors. The low-molecular-weight fraction of the plasma proteome (2,000–10,000 Da range) was analysed by the Matrix-Assisted Laser Desorption Ionisation mass spectrometry. The capacity for DNA break repair was assessed by the comet assay using lymphocytes irradiated in vitro.Results: Spectral components registered in plasma samples were used to build classifiers that discriminated patients from healthy individuals with about 90% specificity and sensitivity (components of 4469, 6929 and 8937 Da were the most essential for cancer classification). Four spectral components were identified (2219, 2454, 3431 and 5308 Da) whose abundances correlated with a maximal intensity of the acute reaction. Several spectral components whose abundances correlated with the rate of DNA repair in irradiated lymphocytes were also detected. Additionally, a more rapid escalation of an acute reaction was correlated with a higher level of unrepaired damage assessed by the comet assay.Conclusions: The plasma proteome could be considered as a potential source of predictive markers of acute reaction in patients with head and neck cancer treated with radiotherapy.

Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2–4 Laryngeal Cancer: Results of a Phase III Randomized Trial

To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

Randomized Clinical Trial on Postoperative Continuous 7-days-a-week Radiotherapy vs. Postoperative Radiochemotherapy in Squamous-cell Head and Neck Cancer: A Report on Acute Normal Tissue Reactions

Conclusions: This study identified a population of patients with multiple potentially HPV-related tumors and demonstrates differ- ent outcomes based on multiple factors, including the site of first diagnosis and duration between diagnoses. Interval between diagnoses was also found to depend upon the site of the initial tumor. In patients presenting with a potentially HPV-related ma- lignancy,anopportunityforsecondarycancerpreventionmayexistthroughbehaviormodificationandalteredscreening, butfuture work is needed to establish true HPV-positivity in this cohort and to understand a potential role for vaccine and chemoprevention strategies. Results: All patients in p-CAIR completed radiotherapy as prescribed, with no need for unplanned interruptions. By contrast, only 59% of the patients in p-CRT received 3 courses of chemotherapy, while cisplatin was discontinued after 2 courses in 37%, and after thefirst coursein4%. Two patientsinp-CRT hadradiation treatmentinterruptions of7 days ormore.Severeadverseeventsin p-CRT included one patient that died due to sepsis (2.4%), one patient with pulmonary embolism (2.4%) and 5 cases of neurotox- icity (12.1%). In addition, 32% of the patients in p-CRT had grade 3 neutropenia, compared to 0% in p-CAIR (p\0.001). The average hemoglobin concentration at the end of radiotherapy was significantly lower in p-CRT compared to p-CAIR (13.5 g/dl vs. 12.0 g/dl, p = 0.02. The platelets count at the end of radiotherapy was lower in p-CRT vs. p-CAIR, but the difference was not sig- nificant (250*10 5 vs. 210*10 5 , p = 0.12). The average maximum total severity score for mucosal reactions was significantly higher in patients treated with p-CAIR compared to p-CRT (15.3 vs. 13.0, p = 0.03). The average duration of severe mucosal reactions (score $10) did not, however, differ significantly in the respective arms (2.9 weeks p-CAIR vs. 2.6 weeks p-CRT). Conclusions: The early tolerance of p-RCT was considerably affected by hematological and neurological reactions that necessi- tated discontinuation of chemotherapy in 41% of the patients. The maximal intensity of acute mucosal reactions was higher in p- CAIR compared to p-RCT, but the duration of severe reactions did not differ significantly between the arms.