Impact of tumour volume and treatment delay on the outcome after linear accelerator-based fractionated stereotactic radiosurgery of uveal melanoma.

BACKGROUND/AIMS: Primary radiation therapy is used to treat malignant uveal melanoma (UM). We report our single-centre experience with fractionated radiosurgery (fSRS) with a linear accelerator (LINAC) after specific adaptation for small target volumes with HybridArc. METHODS: From October 2014 to January 2020, 101 patients referred to Dessau City Hospital with unilateral UM underwent fSRS with 50 Gy given in five fractions on five consecutive days. Primary endpoints were local tumour control, globe preservation, metastasis and death. Potential prognostic features were analysed. Kaplan-Meier analysis, Cox proportional hazards model and linear models were used for calculations. RESULTS: The median baseline tumour diameter was 10.0 mm (range, 3.0-20.0 mm), median tumour thickness 5.0 mm (range, 0.9-15.5 mm) and median gross tumour volume (GTV) 0.4 cm³ (range, 0.2-2.6 cm³). After a median follow-up of 32.0 months (range, 2.5-76.0 months), 7 patients (6.9%) underwent enucleation: 4 (4.0%) due to local recurrence and 3 (3.0%) due to radiation toxicities, and 6 patients (5.9%) revealed tumour persistence with a GTV exceeding 1.0 cm³. Of 20 patients (19.8%) who died, 8 (7.9%) were tumour-related deaths. Twelve patients (11.9%) suffered from distant metastasis. GTV showed an impact on all endpoints, and treatment delay was associated with reduced odds of eye preservation. CONCLUSION: LINAC-based fSRS with static conformal beams combined with dynamic conformal arcs and discrete intensity-modulated radiotherapy results in a high tumour control rate. The tumour volume is the most robust physical prognostic marker for local control and disease progression. Avoiding treatment delay improves outcomes.

Changes of healthy brain tissue after salvage radiotherapy of glioblastoma.

BACKGROUND: Salvage radiotherapy (SRT) with photons is a valid treatment option for patients suffering from recurrent glioblastoma (GBM). However, the tolerance of healthy brain to ionizing radiation (IR) is limited. The aim of this study was to determine to what extent brain structures in the radiographically tumor-free hemisphere change after repeated radiotherapy. METHODS: Five of 26 patients treated with SRT for local recurrence of GBM were found to have magnetic resonance imaging (MRI) studies available for complete volumetric analysis before and after primary chemo-radiation and after SRT. Manual segmentation and joint segmentation (JS) based on a convolutional neural network were used for the segmentation of the gray matter, the white matter and the ventricles in T1 MRIs. RESULTS: Qualitative results of manual segmentation and JS were comparable. After primary chemo-radiation and SRT, the volume of the contralateral ventricles increased steadily by 1.3-4.75% (SD ± 2.8 %, R 2 = 0.82; P = <.01) with a manual segmentation and by 1.4-7.4% (SD 2.1%, R 2 = 0.48; P = .025) with JS. The volume of the cortex decreased by 3.4-7.3% except in one patient, the cortex volume increased by 2.5% (SD ± 2.9%, R 2 = 0.18; P = .19) when measured manually. When measured with JS GM decreased by 1.0-7.4%, in one case it increased by 3.0% (SD = 3.2%, P = .22, R 2 = 0.18). The white matter remained stable when assessed with manual segmentation (P = .84, R 2 = 0.004) or JS (P = .44, R 2 = 0.07). CONCLUSION: SRT of relapsed GBM leads to continuous changes of the tumor-free contralateral brain by means of manual segmentation or JS. The cortex seems more susceptible to repeated RT compared to the white matter. Larger cohort studies and complementary functional analysis are encouraged.

Feasibility of aponeurectomy in combination with perioperative 192Ir high dose rate brachytherapy for Dupuytren's disease.

PURPOSE: Partial aponeurectomy (PA) is a standard procedure for Dupuytren's contracture (DC). Here we report a novel approach using surgery combined with perioperative high dose rate (192Ir-HDR) brachytherapy. METHODS AND PATIENTS: From March 2018 until February 2020, thirteen rays of 6 patients with Dupyutren's contractures underwent PA followed by HDR brachytherapy. After removal of fibrous tissue and mobilization of the tendons, one to three catheters per patient were placed intraoperatively. Immediately after surgery, a planning computer tomography with 3D-planning was performed. Then 10-12 Gy were given to 0-2 mm from the catheters' surface and the catheters were removed 6-12 h after brachytherapy. RESULTS: No complications were observed. The mean contractures were reduced from 55.4° (standard error SE 19.6) to 15.4° (SE 6.7; p < 0.01). One patient showed progressive fibrosis of a nontreated ray during follow-up. CONCLUSIONS: HDR brachytherapy in combination with surgery is feasible and harbors the potential for combined modality therapy to reduce relapse rates of advanced or relapsing DC. Controlled studies are warranted to investigate the role of bimodal therapy compared with PA alone.

Salvage Radiation Therapy for Patients With Relapsing Glioblastoma Multiforme and the Role of Slow Fractionation.

BACKGROUND: Salvage radiation therapy (SRT) can be offered to patients with relapsing glioblastoma multiforme (GBM). Here we report our experience with a schedule extending the treatment time of SRT with the aim to prolong the cytotoxic effect of ionizing radiation while minimizing the cytotoxic hazards for the surrounding brain. METHODS AND PATIENTS: From 2009 until 2017, 124 of 218 patients received radical resection, adjuvant chemo-radiation with photons and temozolomide (TMZ) followed by adjuvant TMZ. Re-irradiation was performed in 26 patients due to local relapse. Treatment schedules varied. Survival and molecular markers were assessed. RESULTS: The median survival was respectively 12 months (9-14.5) of the 124 patients treated with tri-modal therapy and 19.2 months (14.9-24.6) for the 26 patients retreated with SRT (p=0.038). Patients who received daily fractions of 1,6 to 1,65 Gy to a total dose of >40 Gy had a median survival time of 24,6 months compared to patients treated with higher daily doses or a total dose of <40 Gy (p= 0.039), consistent with the observation that patients treated with 21-28 fractions had a median survival of 21,9 months compared to 15,8 months of patients who received 5-20 fractions (p=.0.05). Patients with Ki-67 expression of >30% seemed to perform better than patients with expression levels of ≤20% (p=0.03). MGMT methylation status, TERT promoter or ATRX mutations, overexpression of p53, p16, PD-L1, and EGFR were not prognostic. CONCLUSIONS: Re-irradiation of relapsing GBM is a highly valid treatment option. Our observation challenges hypofractionated stereotactic radiotherapy for retreatment and controlled trials on the fractionation dose for SRT are needed. Robust predictive molecular markers could be beneficial in the selection of patients for SRT.

Pattern of failure after adjuvant radiotherapy following extrapleural pneumonectomy of pleural mesothelioma in the SAKK 17/04 trial.

Postoperative radiotherapy after extrapleural pneumonectomy of malignant pleural mesothelioma was investigated in the randomized phase II trial SAKK17/04. The relapse rate within the high and/or low-dose PTV without previous distant failure was 24%, the isolated in-field-relapse rate within the PTVs was 5% and the distant relapse rate outside of the PTVs was 81%. Clinical outcome was mainly determined by distant disease progression outside of the radiation field.

Optimizing radiosurgery with photons for ocular melanoma.

BACKGROUND AND PURPOSE: Photon radiotherapy has been established for the treatment of ocular melanoma (OM). Here we investigate the planning qualities of two different planning approaches, a combination of dynamic conformal arcs (DCA) complemented with multiple non-coplanar static intensity-modulated (IMRT) fields (DCA-IMRT), and volumetric modulated arc therapy (VMAT) in combination with automated planning (AP). MATERIALS AND METHODS: Thirteen consecutive patients treated for ocular melanoma with curative intent on a Linac-based radiosurgery system were analyzed. Fractionated stereotactic radiosurgery (fSRS) was applied using 50 Gy in 5 fractions using the combination of DCA-IMRT. Plans were reviewed and the thirteen cases were compared to plans obtained with optimized automated VMAT based on a set of 28 distinct patients treated with DCA-IMRT who were selected to generate the AP model for the prediction of dose volume constraints. RESULTS: Overall, plan quality of DCA-IMRT was superior to AP with VMAT. PTV coverage did not exceed 107% in any case treated with DCA-IMRT, compared to seven patients with VMAT. The median PTV covered by >95% was 98.3% (91.9%-99.7%) with DCA-IMRT, compared to 95.1% (91.5%-97.9%) (p < 0.01) with VMAT. The median mean dose delivered to the treated eye was 22.4 Gy (12.3 Gy-33.3 Gy) with DCA-IMRT compared to 27.2 Gy (15.5 Gy-33.7 Gy) (p < 0.01). Dose to the ipsilateral lacrimal gland and the ipsilateral optic nerve were comparable for DCA-IMRT and VMAT, however, the dose to the lens was lower with DCA-IMRT compared to VMAT. CONCLUSIONS: The combination of multiple arcs complemented with multiple IMRT fields sets the gold standard for fSRS of ocular melanoma for photon therapy.

Clinical outcome of postoperative highly conformal versus 3D conformal radiotherapy in patients with malignant pleural mesothelioma.

BACKGROUND: Radiotherapy (RT) is currently under investigation as part of a trimodality treatment of malignant pleural mesothelioma (MPM). The introduction of highly conformal radiotherapy (HCRT) technique improved dose delivery and target coverage in comparison to 3-dimensional conformal radiotherapy (3DCRT). The following study was undertaken to investigate the clinical outcome of both radiation techniques. METHODS: Thirty-nine MPM patients were treated with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant RT. Twenty-five patients were treated with 3DCRT, and 14 with HCRT (Intensity modulated radiotherapy or volumetric modulated arc therapy). Overall survival, disease free survival, locoregional recurrence and pattern of recurrence were assessed. A matched pair analysis was performed including 11 patients of each group. RESULTS: After matching for gender, age, histology, tumor stage and resection status, HCRT seemed superior to 3DCRT with a local relapse rate of 27.3% compared to 72.7% after 3DCRT (p = 0.06). The median time to local relapse was increased by 49% with HCRT in comparison to 3DCRT from 10.9 ± 5.4 months to 16.2 ± 3.1 months (p = 0.06). The median overall survival was 22.3 ± 15.3 months for HCRT and 21.2 ± 9.2 months for 3DCRT (p = 0.57). Recurrence analysis showed that in-field local relapses occurred in previously underdosed regions of the tumor bed in 16% of patients treated with 3DCRT and in 0% of HCRT patients. CONCLUSIONS: The use of HCRT increases the probability of local control as compared to 3DCRT by improving target volume coverage. HCRT did not improve overall survival in this patient series due to the high rate of distant recurrences.

Evaluation of the dosimetric impact of interfractional anatomical variations on prostate proton therapy using daily in-room CT images.

PURPOSE: To quantify interfractional anatomical variations and their dosimetric impact during the course of fractionated proton therapy (PT) of prostate cancer and to assess the robustness of the current treatment planning techniques. METHODS: Simulation and daily in-room CT scans from ten prostate carcinoma patients were analyzed. PT treatment plans (78 Gy in 39 fractions of 2 Gy) were created on the simulation CT, delivering 25 fractions to PTV1 (expanded from prostate and seminal vesicles), followed by 14 boost fractions to PTV2 (expanded from prostate). Plans were subsequently applied to daily CT, with beams aligned to the prostate center in the sagittal plane. For five patients having a sufficiently large daily imaging volume, structure contours were manually drawn, and plans were evaluated for all CT sets. For the other five patients, the plans were evaluated for six selected fractions. The daily CT was matched to the simulation CT through deformable registration. The registration accuracy was validated for each fraction, and the three patients with a large number of accurately registered fractions were used for dose accumulation. RESULTS: In individual fractions, the coverage of the prostate, seminal vesicles, and PTV1 was generally maintained at the corresponding prescription dose. For PTV2, the volume covered by the fractional prescription dose of 2 Gy (i.e., V2) was, on average, reduced by less than 3% compared to the simulation plan. Among the 225 (39 x 5 + 6 x 5) fractions examined, 15 showed a V2 reduction larger than 5%, of which ten were caused by a large variation in rectal gas, and five were due to a prostate shift in the craniocaudal direction. The fractional dose to the anterior rectal wall was found to increase for one patient who had large rectal gas volume in 25 of the 39 fractions, and another who experienced significant prostate volume reduction during the treatment. The fractional bladder dose generally increased with decreasing fullness. In the total accumulated dose for the three patients after excluding a few fractions with inaccurate registration due to a large amount of rectal gas (a condition inconsistent with RTOG protocol), 98.5%, 96.6%, and 98.2% of the PTV2 received the prescription dose of 78 Gy. The V75 and V70 of the anterior rectal wall and bladder both remained within tolerance. CONCLUSIONS: The results confirm that the PT planning techniques and dose constraints used at our institution ensure that target coverage to the prescription dose is maintained in the presence of interfractional anatomical variations. Dose coverage in individual fractions can be compromised, and normal tissue dose increased, due to deviations in the bladder and rectal volume compared to the simulation plans or progressive changes in the prostate volume during the treatment. Deviations from the plan can be reduced with efforts aimed at maintaining consistent daily patient anatomy.

Proton-based radiotherapy for unresectable or incompletely resected osteosarcoma.

BACKGROUND: A study was undertaken to assess clinical outcome and the role of proton therapy for local control of osteosarcoma (OSA). METHODS: All patients who received proton therapy or mixed photon-proton radiotherapy from 1983 to 2009 at the Massachusetts General Hospital were reviewed. Criteria for proton therapy were the need for high dose in the context of highly conformal radiotherapy of unresected or partially resected OSA, positive postoperative margins, postoperative imaging studies with macroscopic disease, or incomplete resection as defined by the surgeon. The primary endpoint was local control of the site treated; secondary endpoints were disease-free survival (DFS), overall survival (OS), long-term toxicity, and prognostic factors associated with clinical outcome. RESULTS: Fifty-five patients with a median age of 29 years (range, 2-76 years) were offered proton therapy. The mean dose was 68.4 gray (Gy; standard deviation, 5.4 Gy). Of the total dose, 58.2% (range, 11%-100%) was delivered with protons. Local control after 3 and 5 years was 82% and 72%, respectively. The distant failure rate was 26% after 3 and 5 years. The 5-year DFS was 65%, and the 5-year OS was 67%. The extent of surgical resection did not correlate with outcome. Risk factors for local failure were ≥ 2 grade disease (P < .0001) and total treatment length (P = .008). Grade 3 to 4 late toxicity was seen in 30.1 % of patients. One patient died from treatment-associated acute lymphocytic leukemia, and 1 from secondary carcinoma of the maxilla. CONCLUSIONS: Proton therapy to deliver high radiotherapy doses allows locally curative treatment for some patients with unresectable or incompletely resected OSA.

Gefitinib in combination with irradiation with or without cisplatin in patients with inoperable stage III non-small cell lung cancer: a phase I trial.

PURPOSE: To establish the feasibility and tolerability of gefitinib (ZD1839, Iressa) with radiation (RT) or concurrent chemoradiation (CRT) with cisplatin (CDDP) in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: In this multicenter Phase I study, 5 patients with unresectable NSCLC received 250 mg gefitinib daily starting 1 week before RT at a dose of 63 Gy (Step 1). After a first safety analysis, 9 patients were treated daily with 250 mg gefitinib plus CRT in the form of RT and weekly CDDP 35 mg/m(2) (Step 2). Gefitinib was maintained for up to 2 years until disease progression or toxicity. RESULTS: Fourteen patients were assessed in the two steps. In Step 1 (five patients were administered only gefitinib and RT), no lung toxicities were seen, and there was no dose-limiting toxicity (DLT). Adverse events were skin and subcutaneous tissue reactions, limited to Grade 1-2. In Step 2, two of nine patients (22.2%) had DLT. One patient suffered from dyspnea and dehydration associated with neutropenic pneumonia, and another showed elevated liver enzymes. In both steps combined, 5 of 14 patients (35.7%) experienced one or more treatment interruptions. CONCLUSIONS: Gefitinib (250 mg daily) in combination with RT and CDDP in patients with Stage III NSCLC is feasible, but CDDP likely enhances toxicity. The impact of gefitinib on survival and disease control as a first-line treatment in combination with RT remains to be determined.

Chemo-radiation with or without mandatory split in anal carcinoma: experiences of two institutions and review of the literature.

BACKGROUND: The split-course schedule of chemo-radiation for anal cancer is controversial. METHODS: Eighty-four patients with invasive anal cancer treated with definitive external beam radiotherapy (RT) with a mandatory split of 12 days (52 patients, Montreal, Canada) or without an intended split (32 patients, Zurich, Switzerland) were reviewed. Total RT doses were 52 Gy (Montreal) or 59.4 Gy (Zurich) given concurrently with 5-FU/MMC. RESULTS: After a mean follow-up of 40 +/- 27 months, overall survival and local tumor control at 5 years were 57% and 78% (Zurich) compared to 67% and 82% (Montreal), respectively. Split duration of patients with or without local relapse was 15 +/- 7 d vs. 14 +/- 7 d (Montreal, NS) and 11 +/- 11 d vs. 5 +/- 7 d (Zurich; P < 0.001). Patients from Zurich with prolonged treatment interruption (> or = 7 d) had impaired cancer-specific survival compared with patients with only minor interruption (<7 d) (P = 0.06). Bowel toxicity was associated with prolonged RT (P = 0.03) duration as well as increased relapse probability (P = 0.05). Skin toxicity correlated with institution and was found in 79% (Montreal) and 28% (Zurich) (P < 0.0001). CONCLUSIONS: The study design did not allow demonstrating a clear difference in efficacy between the treatment regimens with or without short mandatory split. Cause-specific outcome appears to be impaired by unplanned prolonged interruption.

Proton therapy for malignant pleural mesothelioma after extrapleural pleuropneumonectomy.

PURPOSE: To perform comparative planning for intensity-modulated radiotherapy (IMRT) and proton therapy (PT) for malignant pleural mesothelioma after radical surgery. METHODS AND MATERIALS: Eight patients treated with IMRT after extrapleural pleuropneumonectomy (EPP) were replanned for PT, comparing dose homogeneity, target volume coverage, and mean and maximal dose to organs at risk. Feasibility of PT was evaluated regarding the dose distribution with respect to air cavities after EPP. RESULTS: Dose coverage and dose homogeneity of the planning target volume (PTV) were significantly better for PT than for IMRT regarding the volume covered by >95% (V95) for the high-dose PTV. The mean dose to the contralateral kidney, ipsilateral kidney, contralateral lung, liver, and heart and spinal cord dose were significantly reduced with PT compared with IMRT. After EPP, air cavities were common (range, 0-850 cm(3)), decreasing from 0 to 18.5 cm(3)/day. In 2 patients, air cavity changes during RT decreased the generalized equivalent uniform dose (gEUD) in the case of using an a value of < - 10 to the PTV2 to <2 Gy in the presence of changing cavities for PT, and to 40 Gy for IMRT. Small changes were observed for gEUD of PTV1 because PTV1 was reached by the beams before air. CONCLUSION: Both PT and IMRT achieved good target coverage and dose homogeneity. Proton therapy accomplished additional dose sparing of most organs at risk compared with IMRT. Proton therapy dose distributions were more susceptible to changing air cavities, emphasizing the need for adaptive RT and replanning.

Impact of genomic methylation on radiation sensitivity of colorectal carcinoma.

PURPOSE: To investigate the influence of demethylation with 5-aza-cytidine (AZA) on radiation sensitivity and to define the intrinsic radiation sensitivity of methylation deficient colorectal carcinoma cells. METHODS AND MATERIALS: Radiation sensitizing effects of AZA were investigated in four colorectal carcinoma cell lines (HCT116, SW480, L174 T, Co115), defining influence of AZA on proliferation, clonogenic survival, and cell cycling with or without ionizing radiation. The methylation status for cancer or DNA damage response-related genes silenced by promoter methylation was determined. The effect of deletion of the potential target genes (DNMT1, DNMT3b, and double mutants) on radiation sensitivity was analyzed. RESULTS: AZA showed radiation sensitizing properties at >or=1 micromol/l, a concentration that does not interfere with the cell cycle by itself, in all four tested cell lines with a sensitivity-enhancing ratio (SER) of 1.6 to 2.1 (confidence interval [CI] 0.9-3.3). AZA successfully demethylated promoters of p16 and hMLH1, genes associated with ionizing radiation response. Prolonged exposure to low-dose AZA resulted in sustained radiosensitivity if associated with persistent genomic hypomethylation after recovery from AZA. Compared with maternal HCT116 cells, DNMT3b-defcient deficient cells were more sensitive to radiation with a SER of 2.0 (CI 0.9-2.1; p = 0.03), and DNMT3b/DNMT1-/- double-deficient cells showed a SER of 1.6 (CI 0.5-2.7; p = 0.09). CONCLUSIONS: AZA-induced genomic hypomethylation results in enhanced radiation sensitivity in colorectal carcinoma. The mediators leading to sensitization remain unknown. Defining the specific factors associated with radiation sensitization after genomic demethylation may open the way to better targeting for the purpose of radiation sensitization.

Radiation therapy for HIV-associated diffuse large cell non-Hodgkin lymphoma.

PURPOSE: To report the clinical experience with external beam radiotherapy (RT) for AIDS-related lymphoma (ARL) with or without the involvement of the central nervous system (CNS) in HIV-infected patients. PATIENTS AND METHODS: Clinical outcome of 24 HIV-seropositive patients with ARL treated with RT from 1995 to 2004 was reviewed, testing factors associated with outcome. RESULTS: After 1 and 5 years, the overall survival was 65% and 35%, respectively. The mean RT dose was 31 Gy after normalization to fractions of daily 2 Gy (range, 7.8-47.2 Gy). Radiotherapy dose was associated with survival in univariate (P = .04) and multivariate analysis (P = .01). Other factors in univariate analysis associated with outcome were viral load (VL), highly active antiretroviral therapy (HAART), ARL stage, and CNS involvement. Patients with CNS involvement achieved complete response in 46% and improved clinical performance was seen in 73%. CONCLUSIONS: After chemotherapy, RT in combination with HAART is highly active, and RT should be encouraged especially after suboptimal responses to induction treatment.

Cholesteatoma triggering squamous cell carcinoma: case report and literature review of a rare tumor.

BACKGROUND: The aim of this study was to report a case of squamous cell carcinoma of the petrous part of the temporal bone associated with a long history of secondary acquired cholesteatoma in a 71-year-old man. PATIENTS AND METHODS: We present the case of a 71-year-old man diagnosed with secondary acquired cholesteatoma in 1950. Treatments consisted of repetitive surgery owing to several relapses. In 2004, he presented with progressive fetid otorrhea. Clinical and computed tomography findings were indicative for relapsing cholesteatoma and a subtotal petrosectomy was performed. RESULTS: Histologic work-up demonstrated a moderately differentiated squamous cell carcinoma. The staging revealed stadium pT3 cN0 cM0. Postoperative treatment consisted of local radiation therapy with intensity-modulated beam geometry with a total of 64.2 Gy in 30 fractions using a simultaneous integrated boost. CONCLUSION: Middle ear carcinoma can arise from acquired cholesteatoma. The pathogenesis of squamous cell carcinoma associated with cholesteatoma has not been elucidated satisfactorily. Due to the complex anatomic features, intensity-modulated radiation therapy is the technique of choice for postoperative radiotherapy.

High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: results of a survey in EORTC institutes.

OBJECTIVE: Examination of the rate of grade III or grade IV radiation dermatitis during treatment of head and neck cancer (HNC) with radiotherapy (RT) and concurrent cetuximab in EORTC centres. MATERIALS AND METHOD: A questionnaire was sent to all members of the EORTC Radiation Oncology Group and Head and Neck Group (111 institutions) to evaluate the widespread use of cetuximab and radiotherapy in HNC and to estimate the frequency of grades III and IV skin reactions in the radiation portals associated with this protocol. Co-morbidities, RT schedules and co-medications were also recorded. RESULTS: We received responses from 28 institutions in 11 countries. A total of 125 HNC patients from 15 institutions were treated with cetuximab and concurrent RT. Information about the skin reactions was available from 71 patients. Of these 36 had no grade III/IV adverse effects in the RT field, 15 had a grade III and 20 had grade IV radiation dermatitis. No detectable relation of grades III and IV radiation dermatitis with co-morbidities such as liver insufficiency or renal dysfunction was found. CONCLUSION: According to the results of the questionnaire, grade III/IV radiation dermatitis is observed in 49% of HNC patients treated with cetuximab and concurrent RT. A systematic clinical monitoring of cutaneous side effects during RT plus cetuximab is advised to ensure the safety of this protocol.

HIV-specific differences in outcome of squamous cell carcinoma of the anal canal: a multicentric cohort study of HIV-positive patients receiving highly active antiretroviral therapy.

PURPOSE: To define clinical outcome after definitive chemoradiotherapy (CRT) of anal carcinoma in HIV-infected patients treated with highly active antiretroviral therapy (HAART). PATIENTS AND METHODS: A multicentric cohort comparison of 40 HIV-positive patients with HAART and 81 HIV-negative patients treated with radiotherapy (RT) or CRT was retrospectively performed. Local disease control (LC), relapse-free survival (RFS), overall survival (OS), cancer-specific survival (CSS), toxicity, and prognostic factors were investigated. RESULTS: HIV-positive patients were younger (mean age, 48 v 62 years; P < .0005), predominantly male (93% v 25%; P < .0005), and with early-stage (P = .06) and large-cell histology (90% v 67%; P = .005) disease. RT or CRT resulted in complete response in 92% (HIV positive) and 96% (HIV negative) of cases. Five-year OS was 61% (95% CI, 44% to 78%) in HIV-positive and 65% (95% CI, 53% to 77%) in HIV-negative patients (median follow-up, 36 months). Five-year LC was 38% (95% CI, 5% to 71%) in HIV-positive and 87% (95% CI, 79% to 95%) in HIV-negative patients (P = .008) compromising CSS and sphincter preservation. Grade 3/4 acute skin (35% v 17% [HIV negative]; P = .04) and hematologic (33% v 12% [HIV negative]; P = .08) toxicity together approximated 50% in HIV-positive patients. RFS in HIV-positive patients was associated with RT dose (P = .08) and severe acute skin toxicity (P = .04). CONCLUSION: Long-term LC and acute toxicity represent major clinical challenges in HIV-positive patients with anal carcinoma. Even if fluoropyrimidine-based CRT is feasible and may result in similar response rates and OS as in HIV-negative patients, improved treatment strategies with better long-term outcome are warranted.

Combined photon and electron three-dimensional conformal versus intensity-modulated radiotherapy with integrated boost for adjuvant treatment of malignant pleural mesothelioma after pleuropneumonectomy.

PURPOSE: The optimal technique for postoperative radiotherapy (RT) after extrapleural pleuropneumonectomy (EPP) of malignant pleural mesothelioma (MPM) remains debated. METHODS AND MATERIALS: The data from 8 right-sided and 9 left-sided consecutive cases of MPM treated with RT after radical EPP were reviewed. Of the 17 patients, 8 had been treated with three-dimensional (3D) conformal RT (3D-CRT) and 9 with intensity-modulated RT (IMRT) with 6-MV photons. The clinical outcome and adverse events were assessed. For comparative planning, each case was replanned with 3D-CRT using photons and electrons or with IMRT. Homogeneity, doses to the organs at risk, and target volume coverage were analyzed. RESULTS: Both techniques yielded acceptable plans. The dose coverage and homogeneity of IMRT increased by 7.7% for the first planning target volume and 9.7% for the second planning target volume, ensuring >or=95% of the prescribed dose compared with 3D-CRT (p < 0.01). Compared with 3D-CRT, IMRT increased the dose to the contralateral lung, with an increase in the mean lung dose of 7.8 Gy and an increase in the volume receiving 13 Gy and 20 Gy by 20.5% and 7.2%, respectively (p < 0.01). A negligible dose increase to the contralateral kidney and liver was observed. No differences were seen for the spinal cord and ipsilateral kidney. Two adverse events of clinical relevant lung toxicity were observed with IMRT. CONCLUSION: Intensity-modulated RT and 3D-CRT are both suitable for adjuvant RT. IMRT improves the planning target volume coverage but delivered greater doses to the organs at risk. Rigid dose constraints for the lung should be respected.