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We aimed to assess patterns of care delivered to older patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC), and to analyze the use of geriatric assessment (GA) and assessment of quality of life (QoL). Members of the head and neck cancer group and the older task force of the European Organisation for Research and Treatment of Cancer (EORTC), members the European Head and Neck Society and members of national groups in Europe were asked to complete a questionnaire about treatment delivered, use of GA, and QoL assessment in older patients with LA-HNSCC. Investigators from 111 centers replied, including 90 (81.1%) academic centers, 16 (14.4%) community hospitals, and 5 (4.5%) private clinics. Large differences in treatment patterns were found. For instance, for oropharyngeal carcinoma, one third of the centers indicated that they treat <5% of older patients with chemoradiation, while 18 centers (16.2%) treat >40% of older patients with chemoradiation. Fourteen centers (12.6%) routinely perform GA, while 43 centers (38.7%) never do, and 39 centers (35.1%) sometimes do. QoL is assessed on a routine basis in one fifth of the centers. Large differences exist across institutions in the patterns of care delivered to older patients with LA-HNSCC. Prospective studies are required to learn how GA can guide treatment decisions, and how QoL and treatment outcome can be improved. For that, consensus on standard of care is essential. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to evaluate how often distant metastases occur in localized oral squamous cell carcinomas (OSCC). The investigators hypothesize that abdominal sonography and chest X-ray may not be necessary for initial staging of early oral squamous cell carcinoma in UICC stage I/II. Material and methods The investigators implemented a retrospective study. The study collective was composed of 124 patients with OSCC, who were treated in the department of oral and maxillofacial surgery during the years 2011–2015 at the University Medical Center Hamburg Eppendorf, Germany. We focused on age, gender, date of diagnosis, tumour stage (clinical and pathological), HPV status, occurrence of metastases, recurrences, date and frequency of staging and restaging (abdominal sonography, chest X-ray, CT Abdomen/Thorax, PET CT), follow up time and date of death. Descriptive and bivariate statistics were computed (chi-square test) and the P value was set at .05. Results 19 distant metastases were found in 13 out of 124 patients (10.48%). Of those 20 metastases 5 were found in the liver (26.32%), 11 in the lung (57.89%) and 4 in the bone (15.79%). Hepatic metastases co-occurred in every case with pulmonary metastases. In one case bone metastases occurred without the presence of pulmonary metastases. There was no significant correlation of metastasis rate to T stage. But distant metastases were solely found in node positive patients. This was significant for pulmonary metastases, not for liver metastases. Only one out of 11 pulmonary metastases was diagnosed by chest X-ray. Conclusion Abdominal sonography and chest X-ray can be omitted as a standard procedure in staging of localized node negative oral squamous cell carcinoma. A thoracic CT including the liver should be performed in patients with suspected lymph nodes metastases in the neck on CT. A skeletal scintigraphy or alternatively a PET/PET-CT should be added if there are signs and symptoms suspicious for bone metastases. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: When treated by radiotherapy, patients with squamous cell carcinomas of the head and neck (HNSCC) positive for HPV and p16INK4a possess a clearly favorable prognosis as compared to those with HPV-negative HNSCC. The aim of this work was to study whether the better outcomes might be caused by an enhanced cellular radiosensitivity. Materials and methods: The radiation response of five HPV/p16INK4a-positive and five HPV-negative cell lines was characterized with regard to cellular radiosensitivity by colony formation assay. Furthermore G1- and G2-arrest, apoptosis and residual DNA double-strand breaks (DSB) were analyzed by the colcemid-based G1-efflux assay, propidium iodide staining, the detection of PARP cleavage, the fluorescence-based detection of caspase activity and the immunofluorescence staining of γH2AX and 53BP1 foci. Results: On average, the cellular radiosensitivity of the HNSCC cell lines positive for HPV and p16INK4a was higher as compared to the sensitivity of a panel of five HPV-negative HNSCC cell lines (SF3=0.2827 vs. 0.4455). The higher sensitivity does not result from increased apoptosis or the execution of a permanent G1-arrest, but is rather associated with both, elevated levels of residual DSBs and extensive G2-arrest. Conclusions: Increased cellular radiosensitivity due to compromised DNA repair capacity is likely to contribute to the improved outcome of patients with HPV/p16INK4a-positive tumors when treated by radiotherapy. [Copyright &y& Elsevier]

Summary: Objectives: Infection with human papillomavirus (HPV) is linked to oropharyngeal cancer. This analysis investigated possible associations between HPV status, smoking history and survival outcome in patients with neck metastasis and carcinoma of unknown primary (CUP). Materials and methods: Registries at the Universities of Hamburg and Kiel were searched for patients with CUP diagnosed from 2002 to 2011 who had formalin-fixed and paraffin-embedded metastatic lymph node samples available. All patients underwent routine diagnostic procedures to establish the primary site and received radiotherapy (60Gy using conventional fractionation) with or without concurrent cisplatin-based chemotherapy depending on disease extent. Genotyping was performed using polymerase chain reaction; p16[INK4a] expression was assessed using immunohistochemistry. Results: Sixty-three patients were included; 23 (37%) had HPV DNA/p16+ samples and 40 (63%) were negative for either/both markers. A high proportion of patients had a history of tobacco smoking; significantly fewer patients with HPV+/p16+ samples were smokers than those who were negative for either/both markers (61% vs. 90%, respectively; p =0.0067). There were no statistically significant differences between overall or recurrence-free survival in HPV+/p16+ patients vs. those negative for either/both markers. Overall survival appeared to be superior in patients with <10 pack-years smoking history and HPV+/p16+ disease. Conclusions: This study, the largest to date investigating HPV status in head and neck CUP, identified HPV and p16 overexpression in over one-third of patients. Tobacco smoking history appeared to affect survival in HPV+/p16+ patients. Smoking status should be considered as a prognostic factor in patients with CUP, along with HPV DNA status. [ABSTRACT FROM AUTHOR]

Abstract: It has been proposed that p16INK4A qualifies as a surrogate marker for viral oncogene activity in head and neck cancer (HNSCC). By analyzing 78 HNSCC we sought to validate the accuracy of p16INK4A as a reliable marker of active HPV infections in HNSCC. To this end we determined HPV DNA (HPVD) and E6*I mRNA (HPVR) expression status and correlated these results with p16INK4A staining. In tonsillar SCC 12/20 were HPVD+ and 12/12 of these showed active HPV infections whereas in non-tonsillar SCC 10/58 were HPVD+ and 5/10 showed active HPV infections. Thus, we prove about 8% of non-tonsillar SCC to be also correlated with HPV-associated carcinogenesis. Strikingly, 3/14 (21.4%) of tonsillar and non-tonsillar HPVD+/HPVR+ cases did not show p16INK4A overexpression and these cases would have been missed when applying initial p16INK4A staining only. However, in 13 cases negative for HPV, DNA p16INK4A was overexpressed. In conclusion, our data confirm tonsillar SCC to be predominantly but not only associated with active HPV infections. Furthermore, our data show that p16INK4A overexpression is not evident in a subgroup of HNSCC with active HPV infection. Definitive HPV data should therefore be utilized in diagnostics and treatment modalities of HPV positive and HPV negative HNSCC patients, resulting in a paradigm shift regarding these obviously different tumor entities. [Copyright &y& Elsevier]

Summary: Background: Intensity-modulated radiotherapy (IMRT) is a technique that allows delivery of lower doses of radiation to normal tissue, while maintaining or increasing the tumour dose, compared with two-dimensional radiotherapy (2DRT) or three-dimensional conformal radiotherapy (3DCRT). This review of published data was undertaken to assess whether IMRT is associated with quality of life (QoL) benefits versus 2DRT and 3DCRT. Design: English-language literature published between January 2005 and August 2010 was searched for studies comparing IMRT versus 2DRT or 3DCRT in head and neck cancers that included QoL evaluation. Fourteen studies (five prospective and nine retrospective) were identified, two in abstract form only. Only one study was randomised. Studies included patients with nasopharyngeal cancer only, oropharyngeal cancer only and mixed populations. Results: The EORTC QLQ-C30 was the most widely used instrument, generally supplemented with the head and neck cancer module H&N35. IMRT was associated with statistically significant improvements in certain QoL domains versus 2DRT and 3DCRT, particularly those relating to xerostomia, including dry mouth, sticky saliva and eating-related domains. Improvements in global QoL were also observed in the IMRT groups in some studies. Conclusion: Based on the studies reviewed, patients treated with IMRT experience statistically significant improvements in several important QoL domains versus 2DRT and 3DCRT. However, studies included heterogeneous populations, different timepoints for measurements and a variety of instruments for QoL assessment. Accepting the difficulties in execution, IMRT should be compared with 3DCRT in prospective randomised studies in homogeneous patient populations, using appropriate QoL assessments and clinical end points, to establish if IMRT provides enough value for the additional resources involved. [Copyright &y& Elsevier]

Abstract: Studies report an increasing incidence of oropharyngeal cancers linked to infection by human papillomavirus (HPV). We reviewed trials assessing outcomes by HPV DNA status in patients with locally advanced oropharyngeal cancer. Seven of the eight studies identified showed significantly better survival in patients with HPV DNA-positive tumors vs. HPV DNA-negative tumors. The review also describes what needs to be defined regarding optimal treatments. Future trials should incorporate HPV DNA status as a risk determinant and explore treatments for high-risk patients needing therapy intensification, and low- and intermediate-risk patients needing treatment de-intensification to improve tolerability, without compromising survival. [Copyright &y& Elsevier]

Purpose: This prospective, nonrandomized study evaluates the effectiveness of epoetin alfa to maintain the hemoglobin levels at 12 to14 g/dL (optimal range for tumor oxygenation) during chemoradiation for Stage III esophageal cancer and its impact on overall survival (OS), metastatic-free survival (MFS), and locoregional control (LC). Methods and Materials: Ninety-six patients were included. Forty-two patients received epoetin alfa (150 IU/kg, 3 times a week) during radiotherapy, which was started at hemoglobin less than 13 g/dL and stopped at 14 g/dL or higher. Hemoglobin levels were measured weekly during RT. Results: Both groups were balanced for age, sex, performance status, tumor length/location, histology, grading, T-stage/N-stage, chemotherapy, treatment schedule, and hemoglobin before RT. Median change of hemoglobin was +0.3 g/dL/wk with epoetin alfa and −0.5 g/dL/wk without epoetin alfa. At least 60% of hemoglobin levels were 12 to 14 g/dL in 64% and 17% of the patients, respectively (p < 0.001). Patients who received epoetin alfa had better OS (32% vs. 8% at 2 years, p = 0.009) and LC (67% vs. 15% at 2 years, p = 0.001). MFS was not significantly different (42% vs. 18% at 2 years, p = 0.09). Conclusions: The findings suggest that epoetin alfa when used to maintain the hemoglobin levels at 12 to 14 g/dL can improve OS and LC of Stage III esophageal cancer patients. [Copyright &y& Elsevier]

: Purpose:The Radiation Therapy Oncology Group (RTOG) and Late Effects Normal Tissue Task Force subjective, objective, management, and analytic (LENT/SOMA) scores were compared in a group of breast cancer patients. The impact of the classification system on grading late effects was evaluated.: Methods and materials:Telangiectasia, skin pigmentation, and fibrosis were scored according to both LENT/SOMA and RTOG criteria. The results were compared with respect to up- or downgrading and correlated (Spearman’s ρ). Other side effects were recorded using LENT/SOMA criteria. Interobserver variability was calculated with Cohen’s κ. Two hundred fifty-nine subsequent relapse-free patients who underwent breast-conserving therapy between 1981 and 1995 were examined. The median dose of radiotherapy to the breast was 55 Gy. Adjuvant chemotherapy was given to 31 patients and tamoxifen to 52 patients. The median follow-up was 8 years. RTOG skin and s.c. tissue scales and LENT/SOMA breast and pigmentation scales were used. Two doctors examined 45 patients jointly.: Results:Of all patients, 20% had telangiectasia, 22% pigmentation, 43% fibrosis, 4% breast edema, 77% retraction/atrophy, and 54% pain. In comparison, when LENT/SOMA criteria were used, telangiectasia and pigmentation were upgraded in 34% and 36%, respectively, and telangiectasia was downgraded in 45%. Fibrosis correlated well (Spearman’s ρ 0.78, p = 0.01). An additional 356 side effects, mainly retraction/atrophy were observed in 226 patients using LENT/SOMA criteria. Interobserver variability was similar for both classification systems and ranged from Cohen’s κ 0.3 (retraction) to 0.91 (telangiectasia).: Conclusion:LENT/SOMA criteria seem to be the better tool in grading and recording late radiation toxicity compared with the RTOG scale. There was some upgrading with the RTOG score when skin toxicity is evaluated. In contrast, fibrosis scores correlated very well. Adjustments of the LENT/SOMA scoring system should be considered to standardize reporting of late radiation morbidity. [Copyright &y& Elsevier]

Purpose: To evaluate the long-term toxicity after breast-conserving therapy in women with early-stage breast cancer.Methods and Materials: Late toxicity according to the late effects of normal tissue-subjective, objective, management, and analytic (LENT-SOMA) criteria and cosmetic outcome (graded by physicians) were evaluated in 590 of 2943 women with early-stage breast cancer who were irradiated between 1983 and 1995 using the following fractionation schedules: group A, 1983–1987, 2.5 Gy 4x/wk to 60 Gy; group B, 1988–1993, 2.5 Gy 4x/wk to 55 Gy, group C, 1994–1995, 2.0 Gy 5x/wk to 55 Gy.Results: LENT-SOMA Grade 3-4 toxicity was observed as follows: group A (median follow-up 171 months; range 154–222 months), fibrosis 16% (7 of 45), telangiectasia 18% (8 of 45), and atrophy 4% (2 of 45); group B (median follow-up 113 months; range 78–164 months), pain 2% (8 of 345), fibrosis 10% (34 of 345), telangiectasia 10% (33 of 345), arm edema 1% (2 of 345), and atrophy 8% (27 of 345); and group C (median follow-up 75 months, range 51–96 months, n = 200), occurrence of Grade 3-4 late morbidity ≤2%. The cosmetic outcome was very good to acceptable in 78% (35 of 45) of patients in group A, 83% (286 of 345) in group B, and 94% (187 of 200) in group C.Conclusion: In our population, the long-term side effects after breast-conserving therapy were not rare, but were mainly asymptomatic. The LENT-SOMA breast module is a practical tool to assess radiation-induced long-term toxicity. [Copyright &y& Elsevier]

The purpose of this retrospective study was to examine the possible effect of immediate bony microvascular free flap reconstruction of mandibular defects after radical tumor resection of oral squamous cell carcinoma (OSCC) on the rate of local relapse. Our own data regarding recurrence rates for 1-step immediate reconstruction were compared to the published recurrence rates of 2-step reconstructions. A total of 21 patients (aged 45–77 years) with OSCC who underwent a primary surgical therapy with subsequent immediate bony microvascular free flap reconstruction of mandibular defects were followed up for 18–38 months. Four local relapses (19%) were recorded, all in patients with initial tumor stage of T4. Although intraoperative histological findings were R0 in all 21 cases, definitive histology later detected R1 status in the resected bone in 2 cases (10%). Immediate bony free flap reconstruction of mandibular defects after radical surgical resection of OSCC does not seem to increase the risk of local recurrence nor affect patient survival when compared with the 2-step surgical approach. [ABSTRACT FROM AUTHOR]

Aim: Treatment-associated lymphedema is a common side effect after multimodal therapy for locally advanced head and neck cancer (LAHNC). This study aims to evaluate potential prognostic factors for head and neck lymphedema (HNL) and its potential impact on clinical outcome.Methods: This is a prospective data registry analysis on 280 patients treated for locally advanced head and neck cancer (LAHNC). All patients received surgery and risk-adapted platinum-based adjuvant intensity modulated radio(chemo)therapy (R(C)T, IMRT). Treatment- related toxicity was prospectively registered in a data base in regular intervals (baseline 3 months after R(C)T, every 3 months for 3 years, and every 6 months thereafter) and documented according to RTOG/EORTC toxicity criteria.Results: Predictive for any grade HNL 3 months after R(C)T were age, BMI, number of removed nodes and RT modality. Multivariable logistic regression analysis showed that in the acute toxicity phase (3 months after R(C)T) higher body mass index (BMI), extracapsular spread (ECE), linac-based IMRT, bilateral treatment to the neck (surgery and RT), and the addition of chemotherapy increase the risk for grade 2 HNL. For chronic HNL, higher BMI, linac-based IMRT and ECE were predictive for grade 2 HNL. Higher BMI is associated with better local control rates. Advanced age and ECE had a negative impact on OS.Conclusion: HNL is a common acute and late side effect after multimodal therapy for LAHNC. Knowing risk factors for HNL prior to therapy enables caregivers and patients to take measures prior to treatment to prevent or limit the effects of HNL. [ABSTRACT FROM AUTHOR]

The positive prognostic value of HPV-infections in oropharyngeal squamous cell cancer (OSCC) patients has led to the initiation of prospective clinical trials testing the value of treatment de-escalation. It is unclear how to define patients potentially benefiting from de-escalated treatment, whether a positive smoking history impacts survival data and what kind of de-escalation might be best. Here, we investigate the effect of HPV-status, smoking habit and treatment design on overall survival (OS) and progression free survival (PFS) of 126 patients with tonsillar SCC (TSCC) who underwent CO2-laser-surgery and risk adapted adjuvant treatment. HPV-DNA-, HPV-mRNA-, and p16INK4A-expression were analysed and results were correlated to OS and PFS. Factors tested for prognostic value included HPV-status, p16INK4A-protein expression, therapy and smoking habit. Log rank test and p-values ≤0.05 defined significant differences between groups. The highest accuracy of data with highest significance in this study is given when the HPV-RNA-status is considered. Using p16INK4A-expression alone or in combination with HPV-DNA-status, would have misclassified 23 and 7 patients, respectively. Smoking fully abrogates the positive impact of HPV-infection in TSCC on survival. Non-smoking HPV-positive TSCC patients show 10-year OS of 100% and 90.9% PFS when treated with adjuvant RCT. The presented data show that high-precision HPV-detection methods are needed, specifically when treatment decisions are based on the results. Furthermore, smoking habit should be included in all studies and clinical trials testing HPV-associated survival. Adjuvant RCT especially for HPV-positive non-smokers may help to avoid distant failure. [ABSTRACT FROM AUTHOR]

• Quality of life, HPV-status and phase angle predict survival in head and neck cancer patients. • Dental problems at the end of (chemo)radiotherapy influence overall survival in head and neck cancer patients. • HPV negativity is associated with reduced overall survival in head and neck cancer patients. • The baseline phase angle from bioelectric impedance analysis is another predictor of survival. To analyze the impact of quality of life (QoL), nutritional and clinical indicators on overall survival in patients with head and neck squamous cell cancer (HNSCC) undergoing (chemo)radiotherapy. At the beginning, at the end of (chemo)radiotherapy and during follow-up, QoL was prospectively assessed using the EORTC-QLQ-C30 and -QLQ-H&N35 questionnaires. Data were analyzed in 58 out of 220 screened patients, who were randomized into a control and intervention group. All patients received a nutritional assessment including bioelectrical impedance analysis (BIA), laboratory testing, and a screening for malnutrition based on the questionnaires MUST, NRS-2002 and Nutriscore at baseline and at the end of therapy. The intervention consisted of an individualized nutritional counseling every 2 weeks. Except for emotional functioning, dyspnea, financial difficulties, dental problems and weight gain, all other scales from the EORTC-QLQ-C30 and -H&N35 deteriorated during (chemo)radiotherapy. At first follow-up, patients of the control group experienced more nausea and vomiting compared to those of the intervention group (p = 0.02). After performing a multivariable model, dental problems at the end of therapy (HR: 1.03; 95% CI: 1–1.06; p = 0.03), HPV negativity (HR: 18.19, 95% CI: 1.61–204.17; p = 0.02), and baseline phase angle (HR: 0.09; 95% CI: 0.01–0.82; p = 0.03) were identified as predictors for overall survival. Factors influencing overall survival in patients with HNSCC undergoing (chemo)radiotherapy are complex and multifactorial. We were able to identify QoL-related (dental problems), clinical (HPV status) and nutritional (phase angle) factors as negative predictors for survival. This study was registered within the German Clinical Trials Register (DRKS00016862). [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Despite the comparably high cure rates observed for HPV-positive HNSCC, there is still a great need for specific tumor radiosensitization due to the often severe side effects resulting from intense radiochemotherapy. We recently demonstrated that HPV-positive HNSCC cell lines are characterized by a defect in DNA double-strand break repair associated with a pronounced G2-arrest. Here we tested whether abrogation of this radiation-induced G2-arrest by the inhibition of Chk1 results in specific radiosensitization of HPV-positive HNSCC cells. Materials and methods: Experiments were performed with five HPV and p16-positive (93-VU-147T, UM-SCC-47, UT-SCC-45, UD-SCC-2, UPCI-SCC-154) and two HPV and p16-negative HNSCC cell lines, as well as two normal human fibroblast strains. Chk1 was inhibited by the selective inhibitor PF-00477736. Cell cycle distribution was determined by flow cytometry, Chk1-activity via Western blot and cell survival by colony formation assay. Results: With the exception of UPCI-SCC-154, the inhibition of Chk1 was found to abolish the pronounced radiation-induced G2-arrest in all HPV-positive cells utilized. All tumor cell lines that demonstrated the abrogation of G2-arrest also demonstrated radiosensitization. Notably, in G1-arrest-proficient normal human fibroblasts no radiosensitization was induced. Conclusion: Abrogation of the G2 checkpoint through the inhibition of Chk1 may be used to selectively increase the cellular radiosensitivity of HPV-positive HNSCC without affecting the surrounding normal tissue. [Copyright &y& Elsevier]

Purpose: To compare the outcomes of four cisplatin-based radiochemotherapy regimens in 311 patients with Stage III/IV squamous cell carcinoma of the head and neck. Methods and Materials: Concurrent chemotherapy consisted of three courses of cisplatin 100 mg/m2 on Day 1 (Group A, n = 74), two courses of cisplatin 20 mg/m2 on Days 1–5 plus 5-fluorouracil 1,000 mg/m2 on Days 1–5 (Group B, n = 49), two courses of cisplatin 20 mg/m2 on Days 1–5 plus 5-fluorouracil 600 mg/m2 on Days 1–5 (Group C, n = 102), or two courses of cisplatin 20 mg/m2 on Days 1–5 (Group D, n = 86). The groups were retrospectively compared for toxicity and outcomes, and 11 additional factors were evaluated for outcomes. Results: No significant difference was observed among the groups regarding radiation-related acute oral mucositis and radiation-related late toxicities. Acute Grade 3 skin toxicity was significantly more frequent in Group B than in the patients of the other three groups (p = .013). The chemotherapy-related Grade 3 nausea/vomiting rate was 24% for Group A, 8% for Group B, 9% for Group C, and 6% for Group D (p = .003). The corresponding Grade 3 nephrotoxicity rates were 8%, 1%, 2%, and 1% (p = .019). The corresponding Grade 3-4 hematologic toxicity rates were 35%, 41%, 19%, and 21% (p = .027). Chemotherapy could be completed in 50%, 59%, 74%, and 83% of the Group A, B, C, and D patients, respectively (p = .002). Toxicity-related radiotherapy breaks occurred in 39%, 43%, 21%, and 15% of Groups A, B, C, and D, respectively (p = .005). The 3-year locoregional control rate was 67%, 72%, 60%, and 59% for Groups A, B, C, and D, respectively (p = .48). The corresponding 3-year metastasis-free survival rates were 67%, 74%, 63%, and 79% (p = .31), and the corresponding 3-year survival rates were 60%, 63%, 50%, and 71% (p = .056). On multivariate analysis, Karnofsky performance status, histologic grade, T/N category, preradiotherapy hemoglobin level, completion of chemotherapy, and radiotherapy breaks were associated with the outcome. Conclusion: The four compared radiochemotherapy regimens were not significantly different regarding treatment outcomes. Two courses of cisplatin 20 mg/m2 on Days 1–5 were better tolerated than the other three regimens. [Copyright &y& Elsevier]

Background and purpose: To contribute to the question whether the risk of radiation-related brachial plexopathy increases, remains constant or decreases with time after treatment.Patients and methods: Between 12/80 and 9/93, 140 breast cancer patients received supraclavicular lymph node irradiation using a telecobalt unit. Total dose was 60 with 3 Gy per fraction at a depth of 0.5 cm and 52 with 2.6 Gy per fraction to the brachial plexus at a depth of 3 cm. Twenty-eight women received chemotherapy, 34 tamoxifen. Brachial plexopathy was graded using a modified LENT-SOMA score. Actuarial complication-free survival and overall survival were obtained from Kaplan–Meier analysis. The impact of chemotherapy or tamoxifen was tested using the χ2 test. The annual incidence of radiation-related brachial plexopathy was assessed by exponential regression as described by Jung et al. [Radiother Oncol 61 (2001) 233].Results: Actuarial overall survival was 67.1% after 5 years, 54.0% after 10 years, 49.9% after 15 years, and 44.0% after 20 years. In 19/140 patients, brachial plexopathy grade≥1 occurred after a median interval of 88 (30–217) months. The percentage of patients being free from plexopathy was 96.1% after 5 years, 75.5% after 10 years, 72.1% after 15 years, and 46.0% after 19 years, respectively. A significant impact of type of surgery, chemotherapy or tamoxifen was not observed. The annual incidence of brachial plexopathy was 2.9% for grade≥1 lesions and 0.8% for grade≥3 lesions. The rates did not change significantly with time.Conclusions: The risk of brachial plexopathy after supraclavicular lymph node irradiation in breast cancer patients remains constant for a considerable portion of the patient''s life. [Copyright &y& Elsevier]

: PurposeLong-term cosmesis from the patient''s perspective is compared to the doctor''s appraisal. Factors that determine judgment of cosmesis are analyzed. Also, a patient questionnaire was designed to screen for normal tissue reactions and is evaluated.: Methods and patientsWith structured questions, patients rated their satisfaction considering cosmesis, the difference in overall appearance, and specific changes of the breast. Two doctors rated cosmesis and radiation late effects (LENT/SOMA). Ratings were compared, and the relative impact of single items was studied. Two hundred eighty-seven patients with unilateral breast carcinoma were examined after a median follow-up of 8 years. They were treated between 1981 and 1995 with lumpectomy and radiotherapy of the breast with 1.8–2.5 Gy fractions with a median total dose of 55 Gy (range: 50–65 Gy).: ResultsOne hundred sixty-one patients rated cosmesis as satisfying, 73 patients rated it as acceptable, and 25 patients as poor. Eighty-nine patients noted severe changes of appearance. Severe firmness and extensive scars were the most frequent complaint; the most important single item for judging cosmesis as poor was highly visible scars. Generally, doctors rated cosmesis less favorably (satisfactory, 150 patients; poor, 43 patients). Severe fibrosis was more important than discoloration of the breast or scars. Correlation between patients'' and doctors'' rating of cosmesis was modest (Cohen''s weighted kappa 0.29), whereas the doctor''s rating correlated well (0.55). Specificity and sensitivity of the questionnaire item for severe fibrosis (using doctors'' judgments as gold standard) was 0.8; Cohen''s weighted kappa was 0.34 (95% confidence interval: 0.21–0.48).: ConclusionRating of cosmesis is subjective. Patients'' satisfaction with cosmesis is greater than the doctors'' and is determined not only by radiation late effects, but also by factors unrelated to the appearance of the breast. Severe fibrosis may be detected by a patient questionnaire. [Copyright &y& Elsevier]

Objective: Are 6 weekly cycles of cis-Platinum (DDP) plus one cycle of 5-FU with concurrent hyperfractionated radiotherapy (HART) superior to 2 cycles of Mitomycin C (MMC) plus one cycle of 5-FU with HART in terms of overall survival (OS), progression-free (PFS) and metastases-free survival (MFS), local (LC), regional (RC) and loco-regional control (LRC)? Methods: Eligibility: Stage IV SCC of the oro- and hypopharynx (OP and HP), KFS of ⩾80% stratified for sites, N-status, grading, haemoglobin and centres. The HART schedule was reported elsewhere (V.Budach, JCO 23; 2005). HART was applied concurrently with DDP/5-FU at 30mg/m2 days 1, 8, 15, 22, 29 and 36 or MMC/5-FU at 10mg/m2 day 1+36 and for both arms with 600mg/m2 5-FU days 1-5 as 120 hrs. continuous infusion. TVD dose prescription was 72 Gy for macroscopic disease, 60 Gy for surrounding nodes of high-risk and 50 Gy of low-risk for microscopic involvement. 3D-conformal or IMRT-TP was used. 364 patients were analysed using the ITT principle. Hazard ratio (HR) calculations were adjusted for competing risk factors. Results: Median follow-up was 54 mos. for both treatment arms. Mean age was 55.4 years, 83% were males and 17% females. All patients had stage IV at diagnosis (UICC 2002). 58.5% suffered from OP-cancer and 41.5% from HP-cancer. The OS, PFS and MFS at 5 years for the DDP-arm was 39.1%, 47.2% and 66.8% versus 32.8% (n.s.), 37.2% (n.s., HR: 0.74, 95%-CI: 0.55-1.00, p=.05) and 53.5% (p=.044, hazard ratio: 0.63, 95% CI: 0.43-0.94, p=0.023) for the MMC-arm, respectively. The corresponding LC, RC and LRC was 66.2%, 77.3% and 59,1% for the DDP-arm versus 65.9% (n.s), 73.3% (n.s.) and 56.1% (n.s.), for the Mitomycin C arm, respectively. Eight items recorded for acute toxicity (dysphagia, mucositis, dermatitis, xerostomia, pain, weight, leukopenia and creatinine showed no differences between the two treatment arms except for an elevated creatinine level for the DDP-arm (p<.001). Nine items for late morbidity (Dysphagia, Xerostomia, oedema, subcutaneous fibrosis, laryngeal oedema, osteoradionecrosis, plexopathia, L’hermittes syndrome, tracheostomia and PEG showed no significant differences between the treatment arms using nonparametric analyses of variances for repeated measurements. The overall compliance rate for the HART scheme was 96%, DDP: 72%, 5-FU: 97% and MMC: 86%, respectively. Conclusions: This phase III trial first establishes level IB-evidence for a once weekly DDP chemoradiation regimen against two cycles of Mitomycin C. In terms of MFS and DFS @5 yrs., DDP/5-FU HART is superior to MMC/5-FU HART at equal levels of acute and late radiation sequelae for both treatment arms. No significant differences were seen yet for OS, LC, RC or LRC. Chemoradiation with weekly DDP/5-FU or MMC/5-FU shows excellent compliance and can easily compete with other concurrent chemo- or bio-radiation schedules including induction TPF followed by radiation. [Copyright &y& Elsevier]