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Radiation induced atherosclerosis of the carotid artery is a clinically relevant late complication after head and neck radiotherapy. Improved long-term survival after multimodality therapy in neck malignancies result in an increased risk of carotid artery disease in patients after radiotherapy (RT). This review focuses on the current knowledge of occlusive carotid disease after head and neck radiotherapy and highlights the exceeding morphologic post-radiation vessel wall pathologies. More severe and extensive carotid artery atherosclerosis with plaque in all segments including the common carotid artery is a frequent finding after RT. Therefore, colour coded duplex ultrasound surveillance in patients after head and neck RT is recommended. Some histopathological studies indicate differences to “classical” atherosclerosis, and pathogenesis of chronic radiation vasculopathy is still under discussion.

Purpose: The incidence of osteonecrosis of the mandibula (ON) after irradiation using modern three-dimensional planning as well as hyperfractionation or moderately accelerated irradiation has been evaluated and compared with the incidence of the preceding period., Patients and Methods: The records of 268 head and neck cancer patients irradiated between January 1, 1980 and December 31, 1998 with a dose to the mandibula of at least 60 Gy were retrospectively analyzed. All patients had CT-based treatment planning, computerized dose calculation with isodose charts also in several off-axis planes, and regular verification films., Results: The long-term cumulative incidence of ON needing mandibular resection was as follows: after conventional fractionation 6.2% (between 60 and 66.6 Gy target dose) or 20.1% (between > 66.6 and 72 Gy); after hyperfractionated irradiation with a target dose between 72 and 78.8 Gy 6.6%; after concomitant boost irradiation according to the MDA/Houston regime with a dose between 63.9 and 70.5 Gy: no case; after 6 x 2 Gy/week or 7 x 1.8 Gy/week and a total target dose between 66 and 72 Gy approximately 17% or higher (small patient number)., Conclusion: Comparison of the incidence of ON during the period between 1980 and 1990 with the following period between 1990 and 1998 shows a decrease in risk to a value of approximately 5% using modern three-dimensional techniques as well as hyperfractionation or moderately accelerated fractionation.

We summarize the most important developments and innovations in the field over the past years and illustrate resulting external radiation treatment schedules and related treatment tolerance, focusing on hypofractionation. [ABSTRACT FROM AUTHOR]

Background: Volumetric tumor staging has been shown as superior prognostic tool compared to the conventional TNM system in patients undergoing definitive intensity-modulated radiotherapy (IMRT) for head and neck cancer. Recently, clinical immunoscores such as the neutrophil-lymphocyte ratio (NLR) have been investigated as prognostic markers in several tumor entities. The aim of this study was to assess the combined prognostic value of NLR and tumor volume in patients treated with IMRT for oropharyngeal cancer (OC).Methods: Data on all consecutive patients treated for locally advanced or inoperable OC with IMRT from 2002-2011 was prospectively collected. Tumor volume was assessed based on the total gross tumor volume (tGTV) calculated by the treatment planning system volume algorithm. The NLR was collected by a retrospective analysis of differential blood count before initiation of therapy.Results: Overall, 187 eligible patients were treated with a median IMRT dose of 69.6 Gy. Three-year recurrence-free survival (RFS) for low, intermediate, high and very high tumor volume groups was 88%, 74%, 62% and 25%, respectively (p = 0.007). Patients with elevated NLR (>4.68) showed a significantly decreased 3-year RFS of 44% vs. 81% (p < 0.001) and 3-year OS of 56% vs. 84% (p < 0.001). The NLR remained a significant prognostic factor for RFS and OS when tested among tumor volume groups. Univariate and multivariate regression analysis confirmed both tumor volume and NLR as independent prognostic factors. The NLR offered further statistically significant prognostic differentiation of the small/intermediate/large tumor volume groups.Conclusion: The NLR remains an independent prognostic factor for patients with OC undergoing radiotherapy independent of the tumor volume. [ABSTRACT FROM AUTHOR]

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: This study evaluated an automated inverse treatment planning algorithm, Pinnacle Auto-Planning (AP), and compared automatically generated plans with historical plans in a large cohort of head and neck cancer patients.Methods: Fifty consecutive patients treated with volumetric modulated arc therapy (Eclipse, Varian Medical System, Palo Alto, CA) for head and neck were re-planned with AP version 9.10. Only one single cycle of plan optimization using one single template was allowed for AP. The dose to the planning target volumes (PTV's; 3-4 dose levels), the organs at risk (OAR's) and the effective working time for planning was evaluated. Additionally, two experienced radiation oncologists blind-reviewed and ranked 10 plans.Results: Dose coverage and dose homogeneity of the PTV were significantly improved with AP, however manually optimized plans showed significantly improved dose conformity. The mean dose to the parotid glands, oral mucosa, swallowing muscles, dorsal neck tissue and maximal dose to the spinal cord were significantly reduced with AP. In 64 % of the plans, the mean dose to any OAR (spinal cord excluded) was reduced by >20 % with AP in comparison to the manually optimized plans. In 12 % of the plans, the manually optimized plans showed reduced doses by >20 % in at least one OAR. The experienced radiation oncologists preferred the AP plan and the clinical plan in 80 and 20 % of the cases, respectively. The average effective working time was 3.8 min ± 1.1 min in comparison to 48.5 min ± 6.0 min using AP compared to the manually optimized plans, respectively.Conclusion: The evaluated automated planning algorithm achieved highly consistent and significantly improved treatment plans with potentially clinically relevant OAR sparing by >20 % in 64 % of the cases. The effective working time was substantially reduced with Auto-Planning. [ABSTRACT FROM AUTHOR]

Radiation-induced cranial nerve palsy (RICNP) is a severe long-term complication in patients with head and neck cancer following high-dose radiation therapy (RT). We present the case report of a patient with bilateral RICNP of the hypoglossal and vagus cranial nerves (XII/X) following postoperative RT in the era prior to the introduction of intensity-modulated RT (IMRT), and an analysis of our IMRT patient cohort at risk including the case of a XII RICNP. A total of 201 patients whose glosso-pharyngeal (IX), X and XII cranial nerves had been exposed to >65 Gy definitive IMRT in our institution between January, 2002 and December, 2012 with or without systemic therapy, were retrospectively identi- fied. A total of 151 patients out of 201 fulfilling the following criteria were included in the analysis: Locoregionally controlled disease, with a follow-up (FU) of >24 months and >65 Gy exposure of the nerves of interest. So far, one of the assessed 151 IMRT patients at risk exhibited symptoms of RICNP after 6 years. The mean/median FU of the entire cohort was 71/68 months (range, 27-145). The results were compared with literature reports. In conclusion, RICNP appears to be a rare complication. However, a longer FU and a larger sample size are required to draw reliable conclusions on the incidence of RICNP in the era of IMRT. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the role of adjuvant radiotherapy (RT) following nipple-sparing mastectomy (NSM) for patients with ductal carcinoma in situ and invasive breast cancer, based on the published literature. Currently, there is no standard for RT following NSM. NSM aims to spare the nipple areola complex (NAC) without compromising locoregional control. Long-term follow-up studies have begun to show promising results. A search of the English literature was performed using the Medline database and Cochrane central library, with the keywords 'nipple/areola-sparing mastectomy', 'whole skin mastectomy' and 'NAC preservation'. A total of 32 original studies with data on NSM in terms of locoregional control, NAC control, NAC necrosis and adjuvant RT were identified. The median locoregional and NAC recurrence rates were 3.2 and 1.4% (range, 0-28.4% and 0-3.7%), respectively. The volume of remaining breast tissue following NSM was reported inconsistently. In 15 studies, RT was not mentioned. In the remaining 17 studies, RT was administered in 0-100% of patients. Only 7 studies provided detailed information regarding the use of adjuvant RT. Adjuvant thoracic wall irradiation was not used in certain studies, not even for locoregionally advanced tumors. Overall, NSM appears a feasible treatment without increased risk of locoregional recurrence for selected patients. The role of adjuvant RT following NSM requires further clarification. The decision regarding adjuvant RT must be made in interdisciplinary tumor boards and with consideration of the individual situation of the patient. [ABSTRACT FROM AUTHOR]

Background: To analyze the impact of weight loss before and during chemoradiation on survival outcomes in patients with locally advanced head and neck cancer. Methods: From 07/1994-07/2000 a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to either hyperfractionated radiation therapy alone or the same radiation therapy combined with two cycles of concomitant cisplatin. The primary endpoint was time to any treatment failure (TTF); secondary endpoints were locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Patient weight was measured 6 months before treatment, at treatment start and treatment end. Results: The proportion of patients with >5% weight loss was 32% before, and 51% during treatment, and the proportion of patients with >10% weight loss was 12% before, and 17% during treatment. After a median follow-up of 9.5 years (range, 0.1 - 15.4 years) weight loss before treatment was associated with decreased TTF, LRRFS, DMFS, cancer specific survival and OS in a multivariable analysis. However, weight loss during treatment was not associated with survival outcomes. Conclusions: Weight loss before and during chemoradiation was commonly observed. Weight loss before but not during treatment was associated with worse survival. [ABSTRACT FROM AUTHOR]

Background Analysis of the impact of risk factors on survival in patients with oropharyngeal squamous cell carcinoma (OPSCC) treated by primary intensity-modulated radiotherapy (IMRT). Methods One hundred forty patients were included with tissue microarray (TMA) construction and immunohistochemical analysis in 124 patients (87%). Results Survival analysis of patients classified into 3 risk categories according to an algorithm based on p16, smoking, T classification, and N classification revealed significant differences with a low, intermediate, and high-risk group. There was a significant impact of p53 expression as surrogate marker for smoking on outcome. In multivariate analysis, p16-positivity was a positive predictor and alcohol as well as N classification was a negative predictor for survival. The algorithm was modified based on alcohol instead of smoking with even more significant differences between the groups. Conclusions A risk model based on multiple factors instead of p16 as single marker can define different risk groups to select patients for treatment deintensification in future prospective clinical trials. © 2013 Wiley Periodicals, Inc. Head Neck 35: 1698-1706, 2013 [ABSTRACT FROM AUTHOR]

Purpose: Except for early stages (T1/2 N0), the prognosis for patients with oral cavity cancer (OCC) is known to be worse than for those with pharyngeal carcinoma. While definitive intensity modulated radiation therapy (IMRT)-chemotherapy affords loco-regional control rates (LRC) of approximately 80% in advanced pharyngeal cancer, corresponding rates are reported to be much lower for OCC. The aim of this work was to evaluate locoregional disease control and overall survival (OAS) in a relatively large OCC patient cohort treated in the IMRT era. Methods and materials: Between October 2002 and June 2011, 160 OCC patients were treated with curative intention IMRT at our department. 122 patients (76%) were referred with primary disease and 38 patients (24%) with a recurrent OCC at least 3 months after surgery alone. Definitive IMRT was performed in 44/160 patients (28%), whilst 116 patients underwent previous surgery. Simultaneous systemic therapy was administered in 72%. Results: Patients with postoperative IMRT (+/?systemic therapy) with R0-1 status (n = 99) reached significantly higher LRC/OAS rates than patients following IMRT for macroscopic disease (n = 61), with 84%/80% versus 38%/33% at 3 years, respectively (p<0.0001). This was found in patients treated for initial, as well as recurrent, disease. Less than 2% persisting grade 3/4 late effects were observed. Conclusions: IMRT for R0-1 situations translated into a highly significant superior LRC and OAS compared to the IMRT cohort treated for macroscopic disease. Treatment was well tolerated. [ABSTRACT FROM AUTHOR]

Background. This study evaluates the oncological outcome of patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC) after primary radiation therapy ± chemotherapy, primary surgical therapy, and surgical therapy followed by radiation therapy ± chemotherapy. Methods. A total of 156 patients (36%) of a cohort of 427 treated for OPSCC between 1990 and 2006 developed recurrent disease. Fifty-one patients (12%) qualified for salvage treatment. Study endpoints were 5-year overall survival (OS) and disease-specific survival (DSS). Results. The 5-year OS and DSS rates after salvage treatment were 29% and 40%; after initial primary radiation therapy, 25% and 40%; after initial surgery followed by radiation therapy, 40% and 40%; and after initial surgery alone, 20% and 40%. Conclusions. Patients with an advanced OPSCC have a considerable risk for recurrence. Despite poor ultimate outcome, salvage treatment should be attempted in patients with resectable disease, good performance status, and absence of distant metastases. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [ABSTRACT FROM AUTHOR]

Objectives: This study evaluates the oncologic outcome with regard to survival and locoregional tumor control in a cohort of patients with oropharyngeal squamous cell carcinoma (OPSCC) treated according to a uniform algorithm. Study Design: Retrospective chart review. Methods: A total of 427 consecutive patients with OPSCC were treated from 1990 to 2006. Treatment modalities were surgery alone (n = 102), surgery with adjuvant radio(chemo)therapy (n = 159), and primary radio(chemo)therapy (n = 166). Study endpoints were the five-year overall survival (OS) and disease-specific survival (DSS) stratified for primary tumor subsite, stage, T and N category, and age. Results: The five-year OS and DSS for the entire cohort were 57.9% and 68.6%, respectively. OS and DSS for surgery alone were 70.3% and 76.5%, for surgery with radiation 66.6% and 78.9%, and for primary radiation 40.8% and 52.6%, respectively. Survival was significantly better for low stages (stage I/II vs. III/IV), small tumors (T1/2 vs. T3/4), limited nodal involvement (N0/1 vs. N2/3), and younger age at diagnosis. Conclusions: Together with our previous study on quality of life, we were able to show that our selection process gives excellent oncologic outcome in combination with high levels of function and quality of life. Surgery alone for early OPSCC and surgery followed by radiation for advanced OPSCC remain valuable treatment options. Primary radiochemotherapy is a strong alternative for patients who are not candidates for function-preserving surgery. Laryngoscope, 119:534-540, 2009 [ABSTRACT FROM AUTHOR]

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Impact of non-pharmacological innovations on cancer cure rates is difficult to assess. It remains unclear, whether outcome improves with 2- [18-F]-fluoro-2-deoxyglucose-positron emission tomography and integrated computer tomography (PET/CT) and intensity-modulated radiotherapy (IMRT) for curative treatment of advanced pharyngeal carcinoma. Patients and methods: Forty five patients with stage IVA oro- or hypopharyngeal carcinoma were staged with an integrated PET/CT and treated with definitive chemoradiation with IMRT from 2002 until 2005. To estimate the impact of PET/CT with IMRT on outcome, a case-control analysis on all patients with PET/CT and IMRT was done after matching with eighty six patients treated between 1991 and 2001 without PET/CT and 3D-conformal radiotherapy with respect to gender, age, stage, grade, and tumor location with a ratio of 1:2. Median follow-up was eighteen months (range, 6-49 months) for the PET/CT-IMRT group and twenty eight months (range, 1-168 months) for the controls. Results: PET/CT and treatment with IMRT improved cure rates compared to patients without PET/CT and IMRT. Overall survival of patients with PET/CT and IMRT was 97% and 91% at 1 and 2 years respectively, compared to 74% and 54% for patients without PET/CT or IMRT (p = 0.002). The event-free survival rate of PET/CT-IMRT group was 90% and 80% at 1 and 2 years respectively, compared to 72% and 56% in the control group (p = 0.005). Conclusion: PET/CT in combination with IMRT and chemotherapy for pharyngeal carcinoma improve oncological therapy of pharyngeal carcinomas. Long-term follow-up is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Aim of this work was to assess loco-regional disease control in head and neck cancer (HNC) patients treated with postoperative intensity modulated radiation therapy (pIMRT). For comparative purposes, risk features of our series have been analysed with respect to histopathologic adverse factors. Results were compared with an own historic conventional radiation (3DCRT) series, and with 3DCRT and pIMRT data from other centres. Between January 2002 and August 2006, 71 patients were consecutively treated with pIMRT for a squamous cell carcinoma (SCC) of the oropharynx (32), oral cavity (22), hypopharynx (7), larynx (6), paranasal sinus (3), and an unknown primary, respectively. Mean and median follow up was 19 months (2-48), and 17.6 months. 83% were treated with IMRT-chemotherapy. Mean prescribed dose was 66.3 Gy (60-70), delivered with doses per fraction of 2-2.3 Gy, respectively. Results: 2-year local, nodal, and distant control rates were 95%, 91%, and 96%, disease free and overall survival 90% and 83%, respectively. The corresponding survival rates for the subgroup of patients with a follow up time >12 months (n = 43) were 98%, 95%, 98%, 93%, and 88%, respectively. Distribution according to histopathologic risk features revealed 15% and 85% patients with intermediate and high risk, respectively. All loco-regional events occurred in the high risk subgroup. Conclusion: Surgery followed by postoperative IMRT in patients with substantial risk for recurrence resulted in high loco-regional tumor control rates compared with large prospective 3DCRT trials. [ABSTRACT FROM AUTHOR]

Pitch, the rotation around the transversal axis of the patient during radiotherapy has little impact on the dose distribution of small spherical treatment volumes; however it might affect treatment of long volumes requiring a correction with a six degree of freedom couch. We included 10 patients each with nasopharyngeal carcinoma (NPC) and esophageal cancer, treated with volumetric modulated arc therapy. Pitch was simulated by tilting the planning CT in ventral and dorsal direction by ± 1.5° and ± 3°. Verification plans were calculated on the tilted datasets and were compared to the original plan and the dose constraints of the organs at risk (OAR). The deviation in dose to the planning target volume is increasing with the degree of pitch with mean changes of up to 2% for NPC and 1% for esophageal cancer. The most affected OAR in NPC patients are brainstem (max. dose +6.0%) and spinal cord (max. dose +10.0%) when tilted by 3° dorsally and lenses (max. dose +3.3%), oral mucosa (mean dose +2.6%) and parotid glands (mean dose +4.3%) when tilted by 3° ventrally. For esophageal cancer patients, there was no significant change in dose to any OAR. Whereas for esophageal cancer, all tilted treatment plans were still clinically acceptable regarding OAR, 5 NPC plans would no longer be acceptable with a pitch of 1.5° ventral (N = 1), 3° ventral (N = 2) and 3° dorsal (N = 2). Planning target volume coverage in both tumor entities was only slightly affected, but pitch errors could be relevant for OAR in NPC patients. A correction with a six degree of freedom couch is recommended for NPC patients with a pitch mismatch of more than 1.5° to avoid exceeded doses to the OAR. [ABSTRACT FROM AUTHOR]

• Consolidation cetuximab after concurrent triplet radiochemotherapy+cetuximab did not improve the 2-year locoregional control (LRC) rate. • Toxicity was similar in both arms except a tendency for increased late G3/4 mucositis in the arm with consolidation cetuximab. • High serum levels of IL-8, Osteopontin and FasL2 were negatively associated with the primary endpoint 2-year LRC. • The first radiomics model prognostic not only for local control but for combined local and nodal (locoregional) control could be built. • No correlation was found between serum and radiomics markers. Preclinical data suggest that cetuximab should be continued after end of concurrent radiotherapy+cetuximab due to its efficacy against residual tumor cells in the irradiated tumor bed. Based on this concept the phase II add-on cetuximab (AOC) study was designed. Altogether 63 patients with advanced head and neck cancer were treated with radiochemotherapy (70 Gy, cisplatin 40 mg/m2 weekly) in combination with concurrent cetuximab (loading dose 400 mg/m2, then 250 mg/m2 weekly). Thereafter patients were randomized to cetuximab consolidation (500 mg/m2 biweekly × 6) or no further treatment. The primary endpoint was the 2-year locoregional control (LRC) rate. As translational research endpoints serum markers were analyzed before and during treatment and CT-based quantitative image analysis (radiomics) was performed. Median follow-up was 24 months. The 2-year LRC rates were 67.9% and 67.7% in the treatment arms with and without consolidation cetuximab, respectively. Higher than median levels of three serum markers were negatively associated with the 2-year LRC rate in the overall patient cohort: Osteopontin, IL8 and FasL2 (p ≤ 0.05). A radiomics model consisting of two radiomics features could be built showing that higher entropy and higher complexity of tumor Hounsfield unit distribution indicates worse LRC (concordance index 0.66). No correlation was found between biological and imaging markers. There was no evidence that consolidation cetuximab would improve the 2-year LRC rate. Prognostic biological and imaging markers could be identified for the overall patient cohort. Studies with larger patient numbers are needed to correlate biological and imaging markers. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To analyze the prognostic value of clinical tumor response during chemoradiation for locally advanced head and neck cancer. Patients and Methods: The locoregional response at 50.4Gy was assessed by physical examination (PE) in patients treated within the randomized trial SAKK 10/94 using hyperfractionated radiotherapy (RT), median total dose 74.4Gy with or without cisplatin 20mg/m2 chemotherapy on 5 consecutive days during weeks 1 and 5 or 6 of RT. Response was classified as a complete response (CR), complete response with uncertainty (Cru), partial response (PR), stable disease (SD), or progressive disease (PD). The primary endpoint was time to treatment failure (TTF) due to any cause. Secondary endpoints included locoregional-recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Univariate and multivariate Cox proportional hazards (PH) models were applied to analyze the associations between survival endpoints and clinical tumor response. Results: A total of 136, 131 and 97 patients were evaluable for response at the primary tumor, lymph nodes and both sites combined, respectively. At 50.4Gy 57/136 (42%), 46/131 (35%) and 21/97 (22%) patients had a good response (CR/Cru vs. PR/SD) at the primary tumor, the lymph nodes, and both sites combined, respectively. The median follow-up times were 11.4, 9.6 and 11.4years for the three groups. Good responses were all significantly associated with improved TTF, LRRFS, DMFS and OS in univariate analysis whereas good response at the primary tumor and lymph nodes remained significantly associated with TTF and OS after multivariate Cox PH models. Conclusions: Locoregional response at 50.4Gy was identified as predictor of oncologic outcome. PE during treatment should not be underestimated in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To define the best threshold for tumor volume delineation of the (18) fluoro-2-deoxy-glucose positron emission tomography (18FDG-PET) signal for radiotherapy treatment planning of intensity-modulated radiotherapy (IMRT) in head and neck cancer. Methods and Materials: In 25 patients with head-and-neck cancer, CT-based gross tumor volume (GTVCT) was delineated. After PET-CT image fusion, window level (L) was adapted to best fit the GTVCT, and GTVPET was delineated. Tumor maximum (S) and background uptake (B) were measured, and the threshold of the background-subtracted tumor maximum uptake (THR) was used for PET signal segmentation. Gross tumor volumes were expanded to planning target volumes (PTVs) and analyzed. Results: The mean value of S was 40 kBq/mL, S/B ratio was 16, and THR was 26%. The THR correlated with S (r = −0.752), but no correlation between THR and the S/B ratio was seen (r = −0.382). In 77% of cases, S was >30 kBq/mL, and in 23% it was ≤30 kBq/mL, with a mean THR of 21.4% and 41.6%, respectively (p < 0.001). Using PTVPET in radiotherapy treatment planning resulted in a reduced PTV in 72% of cases, while covering 88.2% of GTVCT, comparable to the percentage of GTVPET covered by PTVCT (p = 0.15). Conclusions: A case-specific PET signal threshold is optimal in PET-based radiotherapy treatment planning. Signal gating using a THR of 20% in tumors with S >30% ± 1.6% kBq/mL and 40% in tumors with S ≤30% ± 1.6% kBq/mL is suitable. [Copyright &y& Elsevier]

Abstract: Purpose: To evaluate the outcome after definitive whole pelvis external beam radiotherapy (EBRT) followed by brachytherapy (BT) boost after treatment break vs. external beam boost without break in the treatment of anal carcinoma. Methods and materials: Eighty-one consecutive patients with invasive anal carcinoma were analyzed retrospectively. Patients treated with an interstitial 192Ir high-dose-rate (HDR) implant boost of 14Gy/7 fractions/3d given 3 weeks after completion of whole pelvis 45Gy EBRT were compared with those treated with external beam boost of 14.4Gy, started immediately after completion of whole pelvis 45Gy EBRT. Concomitant chemotherapy (CT) with mitomycin C was applied during whole pelvis EBRT depending on tumor stage. Pattern of care, local disease control (LC), cancer-specific survival (CSS), overall survival (OS), toxicity, and quality of life (QOL) were assessed. Results: Radiotherapy with or without concomitant CT achieved clinical complete response in 93.4% of patients. In early stage tumors, 192Ir-HDR BT boost with CT resulted in a 5-year LC and CSS of 100%. In all patients, BT boost did not result in improved LC, OS, and CSS compared with EBRT boost, despite stage and treatment bias favoring small tumors to be treated with BT. The 5-year and 10-year OS were 66% and 44% (BT boost) and 66% and 52% (EBRT boost), respectively. Subgroup analysis of Stages I and II disease revealed no significant improvement after BT boost compared with EBRT boost. Acute skin toxicity was less common in the BT boost group (whole cohort: p =0.14; Stages I–IIIa: p =0.05), but long-term morbidity and QOL were similar. No local necrosis was seen after BT boost and the 10-year sphincter preservation rate was 87% in these patients. Conclusions: Interstitial 192Ir-HDR implant boost with break and EBRT boost without break yield similar results. Acute skin toxicity is reduced with BT boost but long-term morbidity and QOL are identical. BT boost is most beneficial in early stage tumors but the advantage of BT seems to be limited due to its invasiveness, doctor dependence, and logistic circumstances. [Copyright &y& Elsevier]

Purpose: To assess the outcomes and patterns of failure in solitary plasmacytoma (SP). Methods and Materials: The data from 258 patients with bone (n = 206) or extramedullary (n = 52) SP without evidence of multiple myeloma (MM) were collected. A histopathologic diagnosis was obtained for all patients. Most (n = 214) of the patients received radiotherapy (RT) alone; 34 received chemotherapy and RT, and 8 surgery alone. The median radiation dose was 40 Gy. The median follow-up was 56 months (range 7–245). Results: The median time to MM development was 21 months (range 2–135), with a 5-year probability of 45%. The 5-year overall survival, disease-free survival, and local control rate was 74%, 50%, and 86%, respectively. On multivariate analyses, the favorable factors were younger age and tumor size <4 cm for survival; younger age, extramedullary localization, and RT for disease-free survival; and small tumor and RT for local control. Bone localization was the only predictor of MM development. No dose–response relationship was found for doses >30 Gy, even for larger tumors. Conclusion: Progression to MM remains the main problem. Patients with extramedullary SP had the best outcomes, especially when treated with moderate-dose RT. Chemotherapy and/or novel therapies should be investigated for bone or bulky extramedullary SP. [Copyright &y& Elsevier]

Abstract: To determine whether radiation therapy could be an acceptable alternative to surgery in young patients with adenocarcinoma of the prostate, we analysed the outcome of 39 patients aged under 55 with organ confined tumours who received external radiation therapy in a curative intent. Our results suggest that similar local control in younger and older patients can be expected from either external beam radiotherapy or radical prostatectomy. [Copyright &y& Elsevier]

Purpose: To assess the outcome and prognostic factors in patients with orbital lymphoma treated by radiotherapy (RT).Methods and Materials: Between 1980 and 1999, 90 consecutive patients with primary orbital lymphoma were treated in 13 member institutions of the Rare Cancer Network. A full staging workup was completed in 56 patients. Seventy-eight patients had low-, 6 intermediate-, and 6 high-grade lymphoma, and 75 had a single orbital localization. All patients underwent RT with a median dose of 34.2 Gy (range 4.0-50.4). Eleven patients received chemotherapy in addition to RT.Results: After RT, local control was achieved in 97% of the patients. Local progression occurred in 2% and local relapse 1%. The rate of systemic relapse was 20%, and 9% of the patients developed metachronous contralateral eye involvement. The 5-year disease-free survival, overall survival, and cause-specific survival rate was 65%, 78%, and 87%, respectively. In univariate analyses, the statistically significant favorable prognostic factors were younger age, low grade, normal erythrocyte sedimentation rate, absence of muscular infiltration, complete response to treatment, conjunctival localization, and normal lactate dehydrogenase value for overall survival, disease-free survival, and freedom from treatment failure. In multivariate analysis, the favorable factors were younger age and low grade for overall and disease-free survival; a favorable response, conjunctival localization, and complete staging were highly significant for disease-free survival and freedom from treatment failure. Neither the RT technique nor the total dose influenced the outcome. Cataract and xerophthalmia were the most prominent late toxicities.Conclusion: Moderate- to low-dose RT alone is able to control primary orbital lymphoma with low morbidity. A full staging workup is warranted in these patients. Prognostic factors were identified that could be useful in the overall management of this uncommon site of primary lymphoma. [ABSTRACT FROM AUTHOR]

Purpose: To assess the outcome and patterns of failure in patients with testicular lymphoma treated by chemotherapy (CT) and/or radiation therapy (RT).Methods and Materials: Data from a series of 36 adult patients with Ann Arbor Stage I (n = 21), II (n = 9), III (n = 3), or IV (n = 3) primary testicular lymphoma, consecutively treated between 1980 and 1999, were collected in a retrospective multicenter study by the Rare Cancer Network. Median age was 64 years (range: 21–91 years). Full staging workup (chest X-ray, testicular ultrasound, abdominal ultrasound, and/or thoracoabdominal computer tomography, bone marrow assessment, full blood count, lactate dehydrogenase, and cerebrospinal fluid evaluation) was completed in 18 (50%) patients. All but one patient underwent orchidectomy, and spermatic cord infiltration was found in 9 patients. Most patients (n = 29) had CT, consisting in most cases of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with (n = 17) or without intrathecal CT. External RT was delivered to scrotum alone (n = 12) or testicular, iliac, and para-aortic regions (n = 8). The median RT dose was 31 Gy (range: 20–44 Gy) in a median of 17 fractions (10–24), using a median of 1.8 Gy (range: 1.5–2.5 Gy) per fraction. The median follow-up period was 42 months (range: 6–138 months).Results: After a median period of 11 months (range: 1–76 months), 14 patients presented lymphoma progression, mostly in the central nervous system (CNS) (n = 8). Among the 17 patients who received intrathecal CT, 4 had a CNS relapse (p = NS). No testicular, iliac, or para-aortic relapse was observed in patients receiving RT to these regions. The 5-year overall, lymphoma-specific, and disease-free survival was 47%, 66%, and 43%, respectively. In univariate analyses, statistically significant factors favorably influencing the outcome were early-stage and combined modality treatment. Neither RT technique nor total dose influenced the outcome. Multivariate analysis revealed that the most favorable independent factors predicting the outcome were younger age, early-stage disease, and combined modality treatment.Conclusions: In this multicenter retrospective study, CNS was found to be the principal site of relapse, and no extra-CNS lymphoma progression was observed in the irradiated volumes. More effective CNS prophylaxis, including combined modalities, should be prospectively explored in this uncommon site of extranodal lymphoma. [Copyright &y& Elsevier]