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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

[18FDG] PET-CT-based intensity-modulated radiotherapy treatment planning of head and neck cancer.

PURPOSE: To define the best threshold for tumor volume delineation of the (18) fluoro-2-deoxy-glucose positron emission tomography ((18)FDG-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 (GTV(CT)) was delineated. After PET-CT image fusion, window level (L) was adapted to best fit the GTV(CT), and GTV(PET) 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% +/- 1.6% kBq/mL and 40% in tumors with S

3D-segmentation of the 18F-choline PET signal for target volume definition in radiation therapy of the prostate.

Volumetric assessment of PET signals becomes increasingly relevant for radiotherapy (RT) planning. Here, we investigate the utility of 18F-choline PET signals to serve as a structure for semi-automatic segmentation for forward treatment planning of prostate cancer. 18F-choline PET and CT scans of ten patients with histologically proven prostate cancer without extracapsular growth were acquired using a combined PET/CT scanner. Target volumes were manually delineated on CT images using standard software. Volumes were also obtained from 18F-choline PET images using an asymmetrical segmentation algorithm. PTVs were derived from CT 18F-choline PET based clinical target volumes (CTVs) by automatic expansion and comparative planning was performed. As a read-out for dose given to non-target structures, dose to the rectal wall was assessed. Planning target volumes (PTVs) derived from CT and 18F-choline PET yielded comparable results. Optimal matching of CT and 18F-choline PET derived volumes in the lateral and cranial-caudal directions was obtained using a background-subtracted signal thresholds of 23.0+/-2.6%. In antero-posterior direction, where adaptation compensating for rectal signal overflow was required, optimal matching was achieved with a threshold of 49.5+/-4.6%. 3D-conformal planning with CT or 18F-choline PET resulted in comparable doses to the rectal wall. Choline PET signals of the prostate provide adequate spatial information amendable to standardized asymmetrical region growing algorithms for PET-based target volume definition for external beam RT.

Clinical outcome after treatment with a brachytherapy boost versus external beam boost for anal carcinoma.

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 (192)Ir 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, (192)Ir-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 (192)Ir-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.

Immunization with mutant p53- and K-ras-derived peptides in cancer patients: immune response and clinical outcome.

PURPOSE: To determine the ability to induce tumor-specific immunity with individual mutant K-ras-or p53-derived peptides and to monitor clinical outcome. PATIENTS AND METHODS: Patients in varying stages of disease underwent genetic analysis for mutations in K-ras and p53. Thirty-nine patients were enrolled. Seventeen-mer peptides were custom synthesized to the corresponding mutation. Baseline immunity was assessed for cytotoxic T-lymphocyte (CTL) response and interferon gamma (IFN-gamma) release from mutant peptide-primed lymphocytes. Patients' peripheral-blood mononuclear cells were pulsed with the corresponding peptide, irradiated, and applied intravenously. Patients were observed for CTL, IFN-gamma, interleukin (IL) -2, IL-5, and granulocyte-macrophage colony-stimulating factor responses, for treatment-related toxicity, and for tumor response. RESULTS: No toxicity was observed. Ten (26%) of 38 patients had detectable CTL against mutant p53 or K-ras, and two patients were positive for CTL at baseline. Positive IFN-gamma responses occurred in 16 patients (42%) after vaccination, whereas four patients had positive IFN-gamma reaction before vaccination. Of 29 patients with evident disease, five experienced a period of stable disease. Favorable prognostic markers were detectable CTL activity and a positive IFN-gamma reaction but not IL-5 release. Median survival times of 393 v 98 days for a positive versus negative CTL response (P = .04), respectively, and of 470 v 88 days for a positive versus negative IFN-gamma response (P = .02), respectively, were detected. CONCLUSION: Custom-made peptide vaccination is feasible without any toxicity. CTL and cytokine responses specific to a given mutation can be induced or enhanced with peptide vaccines. Cellular immunity to mutant p53 and K-ras oncopeptides is associated with longer survival.

Radiation therapy and combined modality treatment of gastrointestinal carcinomas.

BACKGROUND: Ionizing radiation (IR) is a potent agent in enhancing tumor control of locally advanced cancer and has been shown to improve disease-free and overall survival in several entities. However, the role of radiotherapy (RT) in the treatment of gastrointestinal tumors remains controversial because of the marked radiation sensitivity of neighboring organs frequently compromising application of high doses of ionizing radiation. METHODS: The Medline and the Cochrane Library from 1980 until 2005 were searched using subject heading (MeSH) terms including "esophageal neoplasm", "gastric neoplasm", "pancreatic neoplasm" and "rectal neoplasm", in combination with the subheadings "radiotherapy", "chemotherapy". The term, "randomized controlled trial", was used to identify randomized trials. The proceedings of the annual meeting of the American Society for Therapeutic Radiology and Oncology from 1999 to 2004 and the annual meeting of the American Society of Clinical Oncology from 1999 until 2005 were searched. Ongoing trials were identified through the Physician Data Query database (www.cancer.gov/search/clinical_trials). RESULTS: RT in combination with surgery enhances tumor control of locally advanced cancer disease and has been shown to improve disease-free and overall survival in rectal cancer. In esophageal adenocarcinoma, survival was prolonged with pre-operative chemo-radiation in a meta-analysis. In gastric cancer, post-operative chemo-radiation can be considered after limited lymphadenectomy. Evidence for improving survival remains to be shown for pancreatic cancer and hepatobiliary carcinoma. In colon cancer, post-operative chemotherapy has proven to prolong survival. The impact of RT seems to be most prominent in the pre-operative setting in patients treated with curative intent. CONCLUSIONS: Pre-operative RT or pre-operative chemo-radiation may be considered in individual cases, but should not be used routinely for gastro-intestinal carcinoma, except for rectal carcinoma. In many studies, pre-operative radiotherapy/chemo-radiation yielded promising results and merits validation in large controlled trials.

Dynamic intensity-modulated non-coplanar arc radiotherapy (INCA) for head and neck cancer.

BACKGROUND AND PURPOSE: To define the potential advantages of intensity-modulated radiotherapy (IMRT) applied using a non-coplanar dynamic arc technique for the treatment of head and neck cancer. MATERIALS AND METHODS: External beam radiotherapy (EBRT) was planned in ten patients with head and neck cancer using coplanar IMRT and non-coplanar arc techniques, termed intensity modulated non-coplanar arc EBRT (INCA). Planning target volumes (PTV1) of first order covered the gross tumor volume and surrounding clinical target volume treated with 68-70 Gy, whereas PTV2 covered the elective lymph nodes with 54-55 Gy using a simultaneous internal boost. Treatment plan comparison between IMRT and INCA was carried out using dose-volume histogram and "equivalent uniform dose" (EUD). RESULTS: INCA resulted in better dose coverage and homogeneity of the PTV1, PTV2, and reduced dose delivered to most of the organs at risk (OAR). For the parotid glands, a reduction of the mean dose of 2.9 (+/- 2.0) Gy was observed (p = 0.002), the mean dose to the larynx was reduced by 6.9 (+/- 2.9) Gy (p = 0.003), the oral mucosa by 2.4 (+/- 1.1) Gy (p < 0.001), and the maximal dose to the spinal cord by 3.2 (+/- 1.7) Gy (p = 0.004). The mean dose to the brain was increased by 3.0 (+/- 1.4) Gy (p = 0.002) and the mean lung dose increased by 0.2 (+/- 0.4) Gy (p = 0.87). The EUD suggested better avoidance of the OAR, except for the lung, and better coverage and dose uniformity were achieved with INCA compared to IMRT. CONCLUSION: Dose delivery accuracy with IMRT using a non-coplanar dynamic arc beam geometry potentially improves treatment of head and neck cancer.

Assessment of 18F PET signals for automatic target volume definition in radiotherapy treatment planning.

INTRODUCTION: Positron emission tomography (PET) alone or in combination with computer tomography (PET/CT) is increasingly used in target volume assessment. A standardized way of converting PET signals into target volumes is not available at present. MATERIALS AND METHODS: Assuming a uniform signal emission from a tumour and surrounding normal tissues, a model-based method was developed to determine a relative threshold level (Th(rel)) for gross tumour volume delineation. Two phantoms consisting of cylindrical and spherical sources of diameter ranging from 4.5 to 43 mm in a tank and (18)F activities ranging from 0.001 to 0.15 MBq/ml for tank and sources, respectively, were used for PET/CT imaging. A Th(rel) was calculated that best corresponded to the physical diameter of the cylindrical sources. Software (SW) was generated to automatically delineate volumes based on this threshold. The SW was validated for in vitro and in vivo PET signals. RESULTS: The Th(rel) best representing the source diameter was 41+/-2.5% (95% confidence level) of the background-subtracted signal. The mean deviation for sources of diameter > or =12.5 mm was < or =1.5 mm. The Th(rel) was constant for diameters > or =12.5 mm. For source diameters <12.5 mm, the 41% level over-estimated the real source diameter by a factor depending on the diameter. In an in vitro set-up the SW was capable of segmenting solitary PET volumes to within 1.4 mm (1SD). For non-homogeneous signals in a clinical set-up minimal manual intervention is presently required to separate target from non-target signals. The SW may slightly underestimate target volumes when compared with CT-based volumes, but works well as a first approximation. The volume can be manually adapted to give the ultimate target volume. CONCLUSIONS: SW-based automatic delineation of the volume of (18)F activity is feasible and highly reproducible. Volumes can be subsequently modified by the clinician if necessary. This approach will increase the efficiency of the planning process.