Comparison of 3D conformal radiation therapy and intensity-modulated radiation therapy in patients with endometrial cancer: efficacy, safety and prognostic analysis.

Introduction: Adjuvant whole-pelvic radiation therapy (WPRT) improves locoregional control for high-intermediate stages I-III endometrial cancer patients. Intensity modulated radiation therapy (IMRT) tends to replace the standard 3D conformal radiation therapy (3DCRT) technique used in trials. Material and methods: Consecutive patients with stages I-IIIc endometrial cancer treated between 2008 and 2014 in our department with post-operative 3DCRT or IMRT WPRT were studied retrospectively. Patients with cervical involvement underwent additional low-dose rate vaginal brachytherapy. The impact of the WPRT technique on local control, tolerance, disease-free survival (DFS) and overall survival (OS) was assessed. Clinicians evaluated routinely acute radiation toxicity each week during radiation therapy and late toxicity during standard follow-up consultations. Results: Median follow-up was 50 months (range: 6-158). Among the 83 patients included, 47 were treated with 3DCRT and 36 with IMRT. There was no difference in patient characteristics between groups. The 5-year locoregional control and DFS rates were 94.5% and 68%, respectively. No significant difference was found between the 3DCRT and IMRT groups in terms of survival, with 5-year OS rates of 74.6% and 78%, respectively. In multivariate analysis, age over 68, stage > T1 and grade 3 were independently associated with shorter DFS and OS. Seven patients (8.4%) had grades 3-4 acute gastrointestinal (GI) toxicity with five patients (10.6%) and two (5.4%) in the 3DCRT and IMRT groups, respectively (p = .69). One case (1.2%) of late grade 3 GI toxicity was observed treated in 3DCRT. Conclusions: IMRT seems to be a safe technique for the treatment of endometrial cancer with a trend towards decreased acute GI toxicities. Results of the phase 3 RTOG 1203 trial are needed to confirm these results.

Efficacy and safety of vinorelbine in heavily pretreated recurrent/metastatic head and neck squamous cell carcinoma patients.

The aim of this study was to evaluate the efficacy and tolerance of vinorelbine as a single agent in the treatment of recurrent/metastatic head and neck squamous cell carcinoma. Patients were treated with oral or intravenous vinorelbine according to the pluridisciplinary tumor board's decision. Efficacy and safety outcomes were analyzed retrospectively. Twenty-three patients were included in the study. Sixteen patients (69%) had received at least two previous lines of chemotherapy. The disease control rate was 19%. The median progression-free survival was 2.6 months and the median overall survival was 3.4 months. The rate of grade 3-4 side effects was low (13%). Only one patient discontinued treatment because of side effects. Vinorelbine seems to be a well-tolerated regimen in heavily pretreated patients. However, this regimen does not seem to be efficient enough to be recommended.

Abdominoperineal resection for squamous cell anal carcinoma: survival and risk factors for recurrence.

BACKGROUND: Despite the results of combined chemoradiation therapy for anal canal squamous cell carcinoma (SCC), up to 30 % of patients will undergo abdominoperineal resection (APR). The aim of this study was to evaluate oncologic outcomes, survival, and recurrence, following APR for anal canal SCC performed in a single center over a 13-year period. METHODS: All patients who underwent APR for anal canal SCC between 1996 and 2009 were retrospectively included. Demographic data, details on treatments, pathological report, and follow-up were noted. Survival curves were plotted using the Kaplan-Meier method and potential prognostic factors were evaluated using Cox proportional hazards models. RESULTS: A total of 105 patients (77 women) were included. Indications for APR included tumor persistence (n = 42; 40 %), recurrence (n = 55; 52.4 %), or a contraindication to radiotherapy (n = 8; 7.6 %). Median follow-up was 33.3 months (range, 1.5-174.3 months). Overall survival and disease-free survival were, respectively, 61 and 48 % at 5 years. In multivariate analysis, tumor stage (T3 or T4), positive margin on pathologic examination and existence of distant metastases at the time of the surgery were associated with a poor prognosis. The indication for APR (persistent vs recurrent disease), gender, concurrent HIV infection, or performance of a VRAM flap did not influence OS or DFS. Overall recurrence rate was 42.6 % (n = 43 of 101). The type of recurrence did not exert a significant effect on survival (p = .4571). CONCLUSION: This study describes the largest single series of APR for anal carcinoma. Major prognostic factors for survival and recurrence were T status and involved margin. The 5-year overall survival was 60 %.

Impact of FDG PET/CT in the staging and the follow-up of anal carcinoma.

PURPOSE: The purpose of the study was to assess the diagnostic performance of positron emission tomography/computed tomography and fluorodeoxyglucose (18F) (FDG PET/CT) for the staging and the follow-up of anal carcinoma, and to evaluate the impact of FDG PET/CT on patient management. MATERIALS AND METHODS: Patients with anal carcinoma were referred to our department from October 2004 until July 2008. The diagnostic performance was evaluated on a perexamination basis and on a per-site basis, together with impact of PET/CT on patient management. The standard of truth was histology when available and, in all cases, follow-up data during at least 6 months. RESULTS: Fifty-eight FDG PET/CT performed in 44 patients were analysed­22 for initial staging and 36 during follow-up. The detection rate of non-excised tumours on initial examination was 93%. During post-treatment follow-up, FDG PET/CT had, on a per-examination basis, sensitivity for the detection of persistent or recurrent disease of 93% and specificity of 81%, and on a per-site basis, 86% and 97%, respectively. Its negative predictive value was 94% on a per-examination basis and 98% on a per-site basis. FDG PET/CT had an impact on management in nine patients out of 44 (20%), which was relevant in eight of them (89%). CONCLUSION: FDG PET/CT is an accurate imaging modality in anal cancer. It has an interesting added value during post-treatment follow-up, especially when persistence or recurrence of disease is suspected. Further studies are needed to evaluate whether surveillance by means of FDG PET/CT might have a positive impact on overall survival.

Impact of (18)F-FDG PET on treatment strategy and 3D radiotherapy planning in non-small cell lung cancer: A prospective multicenter study.

OBJECTIVE: The purpose of our study was to quantify the impact of preradiotherapy (18)F-FDG PET when deciding whether radiotherapy should be curative or palliative in intent and defining its detailed planning in patients with non-small cell lung cancer referred for 3D conformal radical radiotherapy within a large prospective multicenter study. SUBJECTS AND METHODS: Conventional CT and FDG PET were performed 2-3 weeks before radiotherapy was scheduled to start. As an initial step, the medical team was asked to plan radiotherapy while blinded to the results of FDG PET. In a second step, the FDG PET data were revealed, and the medical team had to decide whether or not to confirm their radical radiotherapy strategy and, if so, whether any modifications were required to the treatment plan. RESULTS: Of the 134 patients (79% with stage III disease) who were included in the analysis, 110 patients (82%) had received induction chemotherapy. Prechemotherapy FDG PET also was available for 25 patients. Knowledge of preradiotherapy FDG PET data caused treatment to be cancelled or changed from curative to palliative intent in 15 patients (11%). Of the 119 patients in whom radical radiotherapy was confirmed, the treatment plan was modified in 37 (31%). The concordance rate between the treatment strategies with or without preradiotherapy FDG PET was 62%. Concordance was improved but was still not complete (80%) when the prechemotherapy workup included FDG PET. CONCLUSION: Preradiotherapy FDG PET for non-small cell lung cancer patients referred for 3D conformal radiotherapy may lead to significant modification of treatment strategy and radiotherapy planning.

A comparison of two modalities of stereotactic body radiation therapy for peripheral early-stage non-small cell lung cancer: results of a prospective French study.

OBJECTIVES: This prospective, observational, non-randomized multicentric study was conducted to compare efficiency and toxicity using different modalities of stereotactic body radiation therapy (SBRT) in early-stage peripheral non-small cell lung cancer (NSCLC). METHODS: From 9 April to 11 December, 106 patients were treated according to the local equipment availability for peripheral NSCLC with SBRT: 68 by linear accelerator equipped for SBRT and 38 by Cyberknife®. Multivariate analysis and propensity score analysis using Inverse Probability Treatment Weighting (IPTW) were undertaken in an effort to adjust for potential bias due to non-randomization. RESULTS: 2-year local control rates were 97.0% (95% CI: [90.6%; 99.4%]) with SBRT by Linac vs 100% (95% CI: ([100%; 100%]) with Cyberknife® (p = 0.2839). 2-year PFS and 2-year OS rates were 52.7% (95% CI [39.9%;64.0%]) versus 54.1% (95% CI [36.8; 68.6%]) (p = 0.8582) and 65.1% (95% CI: [51.9%; 75.5%] versus 83.9% (95% CI: [67.5%; 92.4%] (p = 0.0831) using Linac and Cyberknife® respectively. Multivariate regression analysis indicates no significant effect of SBRT treatment type on PFS or OS. Local relapse could not be modeled due to the small number of events (n = 2). Acute and late toxicity rates were not significantly different. After IPTW adjustment, results were unchanged. CONCLUSIONS: No difference in efficiency or toxicity was shown after SBRT of peripheral NSCLC treatment using Linac or Cyberknife®. ADVANCES IN KNOWLEDGE: This is the first large prospective non-randomized study focusing on peripheral localized NSCLC comparing SBRT using an appropriately equipped linac with Cyberknife®. No significant difference in efficiency or toxicity was shown in this situation.

Abdomino-perineal resection for anal cancer: impact of a vertical rectus abdominis myocutaneus flap on survival, recurrence, morbidity, and wound healing.

OBJECTIVES: To evaluate the results of a vertical rectus abdominis myocutaneus (VRAM) flap after abdomino-perineal resection (APR) for anal cancer (AC). BACKGROUND DATA: APR is the only curative treatment for AC that recurs or persists after radiochemotherapy. To obtain a clear surgical margin, APR frequently includes a significant perineal exenteration, leaving a large defect surrounded by irradiated tissue. VRAM may facilitate the healing of such a wound and, by providing tissue that can cover a large defect, can facilitate a wide resection and thus may influence survival. METHODS: All patients who underwent APR for AC between 1996 and 2007 were included. RESULTS: Ninety-five patients (70 women) underwent APR, including 43 patients who subsequently received a VRAM flap. The remaining patients had an omentoplasty. Indications for APR were recurrence of AC (n = 46), persistence of disease (n = 41), and contraindication to radiotherapy (n = 8). The groups (VRAM vs. No VRAM) differed in age at surgery (56.3 vs. 62.1; P = 0.0263); administration of chemotherapy in addition to radiotherapy (81% vs. 59%; P = 0.0218); and stage (ypT3-T4 67.6% vs. 38.4%; P = 0.0394). Five-year overall and disease-free survival did not differ between the 2 groups (58.1% vs. 54.5%; P = 0.6756; 41.1% vs. 48.9%; P = 0.2756). Perineal complications were significantly less frequent following VRAM (26.8% vs. 48.9%; P = 0.0336), with reduced time to healing (18.7 vs. 117 days; P = 0.0019) and the ratio of wound healing to survival time (5.6% vs. 19.4%; P = 0.0176). No difference was observed in the incidence of abdominal incisional hernias (9.3% vs. 9.6%), but patients who underwent a VRAM flap pelvic reconstruction had fewer perineal hernias (0% vs. 15.4%; P = 0.0072). CONCLUSIONS: Survival in the 2 groups was equivalent despite the presence of more advanced cancers in the VRAM flap cohort. This may be explained by the more extensive resections that were performed in this group. VRAM is an effective technique for reducing both the perineal complication rate and wound-healing delay in patients undergoing APR for AC that does not increase abdominal wall morbidity.

Role of "the frame cycle time" in portal dose imaging using an aS500-II EPID.

INTRODUCTION: This paper evaluates the role of an acquisition parameter, the frame cycle time "FCT", in the performance of an aS500-II EPID. MATERIALS AND METHODS: The work presented rests on the study of the Varian EPID aS500-II and the image acquisition system 3 (IAS3). We are interested in integrated acquisition using asynchronous mode. For better understanding the image acquisition operation, we investigated the influence of the "frame cycle time" on the speed of acquisition, the pixel value of the averaged gray-scale frame and the noise, using 6 and 15MV X-ray beams and dose rates of 1-6Gy/min on 2100 C/D Linacs. RESULTS: In the integrated mode not synchronized to beam pulses, only one parameter the frame cycle time "FCT" influences the pixel value. The pixel value of the averaged gray-scale frame is proportional to this parameter. When the FCT <55ms (speed of acquisition V(f/s)>18 frames/s), the speed of acquisition becomes unstable and leads to a fluctuation of the portal dose response. A timing instability and saturation are detected when the dose per frame exceeds 1.53MU/frame. Rules were deduced to avoid saturation and to optimize this dosimetric mode. CONCLUSION: The choice of the acquisition parameter is essential for the accurate portal dose imaging.

Growth inhibition by STI571 in combination with radiation in human chronic myelogenous leukemia K562 cells.

Altered radiation responses by STI571 (Imatinib, Glivec), a specific inhibitor of the tyrosine kinase activity of Bcr-Abl, was assessed in K562 chronic myelogenous leukemia cells using growth inhibition and colony formation assays. Flow cytometry, Western blotting, and microscope observation were used to determine cell cycle redistribution, erythroid differentiation, apoptosis, necrosis, senescence, and expression and phosphorylation of effectors downstream from Bcr-Abl as endpoints. STI571 (> or =24-h contact) retarded the growth of K562 cells and elicited reduction in the G(2)-phase content due to an efficient arrest in early S phase rather than to the disruption of the G(2) checkpoint as confirmed by analysis of Lyn and CDK1 phosphorylation. STI571 brought about the inhibitory dephosphorylation of Bcr-Abl and STAT5, but the expression of DNA-PKcs and Rad51 was unaffected and the interaction between radiation and STI571 was strictly additive with regard to induction of apoptosis. Overall STI571 interacted cooperatively with radiation to retard the growth of K562 cells but did not affect intrinsic radiosensitivity. However, STI571 and radiation acted antagonistically with each other with regard to induction of senescence and erythroid differentiation.

Radiosurgery with or without A 2-mm margin for 93 single brain metastases.

PURPOSE: Retrospective comparison of Linac radiosurgery (RS) in 93 single brain metastases with or without a 2-mm margin. PATIENTS AND METHODS: A total of 153 patients had Linac RS (between April 1992 and June 2004), with 139 patients (90.8%) evaluable in June 2005. Sixty-one patients (44%) had extracranial lesions and 65 patients had neurologic symptoms (47%). RS alone: 105 patients (66%); RS +whole brain radiotherapy: 34 patients (24%). Single metastasis: 93/139 patients; classic RS: 42/93 patients; 2-mm margin: 51/93 patients; 30 multiple lesions patients were excluded. TREATMENT: 15 Mv X-ray Linac, circular minibeams, 8-30 mm, four to six noncoplanar coronal arcs. Isodose was 60-80%; doses were 10-20 Gy. FOLLOW-UP: 12 months-13 years; median, 14 months. RESULTS: Local control (LC) was not improved in 51 margin patients vs. 42 classic RS patients: 1 year: 69.1% and 72.4%. Two-year LC rate: 64% and 54.7%, respectively. Survival: median classic RS: 11.3 months; margin RS, 19 months (p = 0.34) and 1 year, 41.6% and 60.2%, respectively. Margin RS patients had a significantly higher rate of severe parenchymal complications: 19.6% vs. 7.1% (p = 0.02); surgery was necessary in 4 of 51 cases vs. 1 of 42 classic RS cases. CONCLUSION: No increase of 1- and 2-year LC rate in margin RS or survival and median survival: 11.3 vs. 19 months (NS) 2-mm margin associated with more severe parenchymal complications (p = 0.02). This procedure is therefore not recommended. Late CT images and 1-mm margin as recommended by pathologists, use of three-dimensional magnetic resonance imaging and fuzzy method to calculate volumes may yield better results. Stereotactic hypofractionation requires further studies.

External validation of leukocytosis and neutrophilia as a prognostic marker in anal carcinoma treated with definitive chemoradiation.

PURPOSE: To validate the prognostic value of leukocyte disorders in anal squamous cell carcinoma (SCC) patients receiving definitive concurrent chemoradiation. MATERIALS AND METHODS: Bi-institutional clinical records from consecutive patients treated between 2001 and 2015 with definitive chemoradiation for anal SCC were retrospectively reviewed. Prognostic value of pretreatment leukocyte disorders was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as leukocyte or neutrophil count exceeding 10G/L and 7G/L, respectively. RESULTS: We identified 133 patients, treated in two institutions. Eight% and 7% displayed baseline leukocytosis and neutrophilia, respectively. Estimated 3-year overall survival (OS) and progression-free survival (PFS) were 88% and 77%, respectively. In univariate analysis, both leukocytosis and neutrophilia were associated with worse OS, PFS (p<0.01), locoregional control (LRC) and Distant Metastasis Control (DMC) (p<0.05), also after stratification by each institution. In multivariate analysis, leukocytosis and neutrophilia remained as independent risk factors associated with poorer OS, PFS, LRC and DMC (p<0.05). CONCLUSION: This study validates leukocytosis and neutrophilia as independent prognostic factors in anal SCC patients treated with definitive chemoradiation. Although prospective confirmation is warranted, it is suggested that the leukocyte and neutrophil count parameters are clinically relevant biomarkers to be considered for further clinical investigations.

[PET and malignant cerebral tumors]. / La TEP dans les tumeurs malignes cérébrales.

Normal biodistribution of FDG includes intense physiologic uptake in the brain, which consumes glucose. The high background therefore makes it difficult to detect the foci taking up glucose, which correspond to malignant lesions. FDG PET is nevertheless clinically useful for detecting high-grade gliomas, cerebral lymphomas and, in some cases, unexpected brain metastases in whole-body PET examinations. As an adjunct to CT and MRI, FDG-PET can make stereotactic radiosurgery more precise in targeting primary or secondary brain cancers and can differentiate necrotic fibrosis from viable cancer tissue during follow-up in cases of abnormal or equivocal MRI results. When available, methionine-(11C) PET delineates low grade gliomas accurately. Several fluorine (18F)-labeled radiopharmaceuticals have been proposed in this setting, with FET and FDOPA apparently the most effective. Four original clinical cases illustrating performances of FET and FDOPA PET in this setting are presented.

[Stage IB2, IIA and IIB cervical carcinoma without lymph node extension treated with neoadjuvant chemoradiotherapy]. / Cancers du col utérin de stade IB2, IIA et IIB sans extension ganglionnaire traités par chimioradiothérapie préopératoire.

PURPOSE: To evaluate the results of preoperative chemoradiation for resectable bulky cervical carcinoma without lymph node involvement after surgical lymph node staging. PATIENTS AND METHODS: Between 2000 and 2010, 45 patients with cervical carcinoma stage IB2 (11 patients), IIA2 (3 patients) and IIB with proximal parametrial invasion (31 patients) were treated with pelvic radiation therapy at a dose of 40.5Gy and concurrent platin (44 patients) or mitomycin (one patient). Forty-two patients had low-dose-rate preoperative uterovaginal brachytherapy at a dose of 20Gy. All patients underwent hysterectomy. Three patients had postoperative low-dose-rate vaginal brachytherapy at a dose of 20Gy. The median follow-up was 34 months. RESULTS: A pathologic cervical residual tumor was observed in 16 patients (35.6%). Six patients presented a relapse (13.3%) with a median delay of 8 months. The 5-year overall survival and disease free survival rates were 88.4% and 84.7%, respectively. In univariable analysis, a cervical residual tumor was the only predictive factor of overall survival (P=0.03). Late toxicity was observed in seven patients. CONCLUSION: Chemoradiation followed by surgery for resectable bulky stage I-II cervical carcinoma without lymph node involvement on pretreatment surgical staging can be used with a good local control and a high rate of 5-year overall survival.

Chemoradiation in rectal squamous cell carcinoma: Bi-institutional case series.

BACKGROUND AND PURPOSE: Primary rectal squamous cell carcinoma (SCC) is an uncommon disease. Early reports stated that surgery is the most effective treatment. However, recent publications suggest conservative strategy with chemoradiation provides satisfactory results. PATIENTS AND METHODS: We have retrospectively studied the medical charts of 23 patients treated for a rectal SCC in two teaching hospitals in France between 1992 and 2013. Twenty-one patients received an exclusive chemoradiotherapy (CRT) and two a pre-operative CRT followed by a planned surgery. Patients received pelvic irradiation with a dose ranging from 36-45 Gy followed by a boost of 15-23 Gy. Twenty-two patients received a concurrent chemotherapy. RESULTS: After CRT, the rate of clinical complete response was 83%. With a median follow-up of 85 months, 5-year overall survival rate was 86%. Five patients presented with a relapse. The 5-year disease-free survival rate was 81%. The 5-year colostomy-free survival rate was 65%. Three patients (13%) presented with grade III-IV late rectal toxicity. CONCLUSIONS: Although retrospective, this is the largest cohort of patients treated with CRT for a rectal SCC. Exclusive CRT could result in high local control rate and prolonged survival in rectal SCC patients with a high rate of organ preservation.

Anal canal carcinoma: early-stage tumors < or =10 mm (T1 or Tis): therapeutic options and original pattern of local failure after radiotherapy.

PURPOSE: To investigate the clinical history, management, and pattern of recurrence of very early-stage anal canal cancer in a French retrospective survey. METHODS: The study group consisted of 69 patients with Stage Tis and T1 anal canal carcinoma < or =1 cm treated between 1990 and 2000 (12 were in situ, 57 invasive, 66 Stage N0, and 3 Stage N1). The median patient age was 67 years (range, 27-83 years). Of the 69 patients, 66 received radiotherapy (RT) and 3 with in situ disease were treated by local excision alone without RT. Twenty-six patients underwent local excision before RT (12 with negative and 14 with positive surgical margins). Of the 66 patients who underwent RT, 8 underwent brachytherapy alone (median dose, 55 Gy), 38 underwent external beam RT (median dose, 45 Gy) plus a brachytherapy boost (median boost dose, 20 Gy), and 20 underwent external beam RT alone (median dose, 55 Gy). RESULTS: Of the 69 patients, 68 had initial local control. Of the 66 patients treated by RT, 6 developed local recurrence at a median interval of 50 months (range, 13-78 months). Four patients developed local failure outside the initial tumor bed. Of the 3 patients with Tis treated by excision alone, 1 developed local recurrence. No relation was found among prior excision, dose, and local failure. The 5-year overall survival, colostomy-free survival, and disease-free survival rate was 94%, 85%, and 89%, respectively. The rate of late complications (Grade 1-3) was 28% and was 14% for those who received doses <60 Gy and 37% for those who received doses of > or =60 Gy (p = 0.04). CONCLUSION: Most recurrences occurred after a long disease-free interval after treatment and often outside the initial tumor site. These small anal cancers could be treated by RT using a small volume and moderate dose (40-50 Gy for subclinical lesions and 50-60 Gy for T1).

Impact of computed tomography and 18F-deoxyglucose coincidence detection emission tomography image fusion for optimization of conformal radiotherapy in non-small-cell lung cancer.

PURPOSE: To report a retrospective study concerning the impact of fused 18F-fluoro-deoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and CT images on three-dimensional conformal radiotherapy planning for patients with non-small-cell lung cancer. METHODS AND MATERIALS: A total of 101 patients consecutively treated for Stage I-III non-small-cell lung cancer were studied. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same treatment position. Images were coregistered using five fiducial markers. Target volume delineation was initially performed on the CT images, and the corresponding FDG-PET data were subsequently used as an overlay to the CT data to define the target volume. RESULTS: 18F-fluoro-deoxy-D-glucose-PET identified previously undetected distant metastatic disease in 8 patients, making them ineligible for curative conformal radiotherapy (1 patient presented with some positive uptake corresponding to concomitant pulmonary tuberculosis). Another patient was ineligible for curative treatment because the fused PET-CT images demonstrated excessively extensive intrathoracic disease. The gross tumor volume (GTV) was decreased by CT-PET image fusion in 21 patients (23%) and was increased in 24 patients (26%). The GTV reduction was > or = 25% in 7 patients because CT-PET image fusion reduced the pulmonary GTV in 6 patients (3 patients with atelectasis) and the mediastinal nodal GTV in 1 patient. The GTV increase was > or = 25% in 14 patients owing to an increase in the pulmonary GTV in 11 patients (4 patients with atelectasis) and detection of occult mediastinal lymph node involvement in 3 patients. Of 81 patients receiving a total dose of > or = 60 Gy at the International Commission on Radiation Units and Measurements point, after CT-PET image fusion, the percentage of total lung volume receiving >20 Gy increased in 15 cases and decreased in 22. The percentage of total heart volume receiving >36 Gy increased in 8 patients and decreased in 14. The spinal cord volume receiving at least 45 Gy (2 patients) decreased. Multivariate analysis showed that tumor with atelectasis was the single independent factor that resulted in a significant effect on the modification of the size of the GTV by FDG-PET: tumor with atelectasis (with vs. without atelectasis, p = 0.0001). CONCLUSION: The results of our study have confirmed that integrated hybrid PET/CT in the treatment position and coregistered images have an impact on treatment planning and management of non-small-cell lung cancer. However, FDG images using dedicated PET scanners and respiration-gated acquisition protocols could improve the PET-CT image coregistration. Furthermore, the impact on treatment outcome remains to be demonstrated.

Impact of CT and 18F-deoxyglucose positron emission tomography image fusion for conformal radiotherapy in esophageal carcinoma.

PURPOSE: To study the impact of fused (18)F-fluoro-deoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and computed tomography (CT) images on conformal radiotherapy planning for esophageal carcinoma patients. METHODS AND MATERIALS: Thirty-four esophageal carcinoma patients were referred for concomitant radiotherapy and chemotherapy with radical intent. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same treatment position. PET images were coregistered using five fiducial markers. Target delineation was initially performed on CT images, and the corresponding PET data were subsequently used as an overlay to CT data to define the target volume. RESULTS: (18)F-fluorodeoxy-D-glucose-PET identified previously undetected distant metastatic disease in 2 patients, making them ineligible for curative conformal radiotherapy. The gross tumor volume (GTV) was decreased by CT and FDG image fusion in 12 patients (35%) and increased in 7 patients (21%). The GTV reduction was > or =25% in 4 patients owing to a reduction in the length of the esophageal tumor. The GTV increase was > or =25% with FDG-PET in 2 patients owing to the detection of occult mediastinal lymph node involvement in 1 patient and an increased length of the esophageal tumor in 1 patient. Modifications of the GTV affected the planning treatment volume in 18 patients. Modifications of the delineation of the GTV and displacement of the isocenter of the planning treatment volume by FDG-PET also affected the percentage of total lung volume receiving >20 Gy in 25 patients (74%), with a dose reduction in 12 patients and dose increase in 13. CONCLUSION: In our study, CT and FDG-PET image fusion appeared to have an impact on treatment planning and management of esophageal carcinoma. The affect on treatment outcome remains to be demonstrated.

Combined chemotherapy and preoperative irradiation for locally advanced noninflammatory breast cancer: updated results in a series of 120 patients.

PURPOSE: To evaluate our updated data concerning survival and locoregional control in a prospective study of locally advanced noninflammatory breast cancer (LABC) after primary chemotherapy (CT) followed by external preoperative irradiation (RT). METHODS AND MATERIALS: Between 1982 and 1998, 120 patients (75 Stage IIIA, 41 Stage IIIB, and 4 Stage IIIC according to AJCC staging system 2002) were treated by four courses of induction CT with anthracycline-containing combinations followed by preoperative RT (45 Gy to the breast and nodal areas) and a fifth course of CT. Three different locoregional approaches were proposed depending on tumor characteristics and tumor response. After completion of local therapy, all patients received a sixth course of CT and a maintenance adjuvant CT regimen without anthracycline. The median follow-up from the beginning of treatment was 140 months. RESULTS: Mastectomy and axillary dissection were performed in 49 patients (with residual tumor larger than 3 cm in diameter or located behind the nipple or with bifocal tumor), and conservative treatment in 71 patients (39 achieved clinical complete response or partial response >90% and received additional radiation boost to initial tumor bed; 32 had residual mass < or =3 cm in diameter and were treated by wide excision and axillary dissection followed by a boost to the excision site). Ten-year actuarial local failure rate was 13% after RT alone, 23% after wide excision and RT, and 4% after mastectomy (p = 0.1). After multivariate analysis, possibility of breast-conserving therapy was related to initial tumor size (<6 cm vs. > or =6 cm in diameter, p = 0.002). Ten-year overall metastatic disease-free survival rate was 61%. After multivariate analysis, metastatic disease-free survival rates were significantly influenced by clinical stage (Stage IIIA-B vs. IIIC, p = 0.0003), N-stage (N0 vs. N1-2a, and 3c, p = 0.017), initial tumor size (<6 cm vs. > or =6 cm in diameter, p = 0.008), and tumor response after induction CT and preoperative RT (clinically complete response + partial response vs. nonresponder, p = 0.0015). In the nonconservative breast treatment group, of the 32 patients with no change in clinical tumor size after induction CT, the 10-year metastatic disease-free survival rate was 59% with only one local relapse. Arm lymphedema was noted in 17% (14 of 81) after axillary dissection and in 2.5% (1 of 39) without axillary dissection. Cosmetic results were satisfactory in 70% of patients treated by RT alone and in 51.5% of patients after wide excision and RT. CONCLUSION: Despite the poor prognosis of patients with LABC resistant to primary anthracycline-based regimen, aggressive locoregional management using preoperative RT and mastectomy with axillary dissection offers a possibility of long-term survival with low local failure rate for patients without extensive nodal disease. On the other hand, the rate of local failure seems to be high in patients with clinical partial tumor response after induction CT and breast-conserving treatment combining preoperative RT and large wide excision.

Results of definitive irradiation in a series of 305 epidermoid carcinomas of the anal canal.

PURPOSE: To evaluate our data concerning the prognostic factors for locoregional control, survival, late complications, and sphincter conservation in a series of epidermoid cancers of the anal canal without clinical evidence of metastasis. METHODS AND MATERIALS: Between June 1972 and January 1997, 305 patients were treated with curative-intent radiotherapy (RT). The T stage according to the 1987 International Union Against Cancer classification was T1 in 26, T2 in 141, T3 in 104, and T4 in 34. Forty-nine patients had nodal involvement at presentation. The pretreatment anal function score, according to our in-house system, was 0 for 22 patients, 1 for 182, 2 for 74, 3 for 7, and 4 for 11 patients; for 9 patients, scores were unavailable. The treatment started with external beam radiotherapy (EBRT) in 303 patients (median dose 45 Gy). After a rest period of 4-6 weeks, a boost of 20 Gy was delivered by EBRT in 279 patients and by interstitial (192)Ir brachytherapy in 17 patients. Seven patients received only one course of EBRT (mean dose 49.5 Gy), and 2 patients were treated with interstitial (192)Ir brachytherapy alone (55 Gy and 60 Gy). Concomitant chemotherapy (5-fluorouracil and either mitomycin C or cisplatin) was delivered to 19 patients. The mean follow-up was 103 months (median 84). RESULTS: At the end of RT, the local tumor clinical complete response rate was 96% for T1, 87% for T2, 79% for T3, and 44% for T4. Of the 61 locally progressive tumors, 27 (44%) were salvaged with abdominoperineal resection. The rate of local tumor relapse was 12%. Among 37 local tumor relapses, 20 (54%) were salvaged with abdominoperineal resection and one with interstitial (192)Ir brachytherapy. The overall local control rate (with or without salvage local therapy) was 84%. The local control rate with good anal function (score 0 or 1) was 56.5%. Of 181 available patients with their anus preserved, 94% had good anal function. For a subgroup of 15 patients with a tumor length of <2 cm and without nodal involvement, the clinical complete response rate after RT completion was 100%, the local control rate with or without local salvage treatment was 100%, and among 13 available patients with their anus preserved, the anal function score was good in 12 patients (92%). The 10-year disease-free survival rate was 74%. After multivariate analysis, three independent predictive factors significantly influenced disease-free survival: the interval between the two courses of RT (>38 days vs. < or =38 days, p = 0.0025), pretreatment anal function score (0 vs. 1 vs. 2 vs. 3 vs. 4, p = 4.4.10(-6)), and clinical complete response after RT completion (no complete response vs. complete response, p = 2.5.10(-14)). CONCLUSION: We confirm the excellent results with RT in T1 and T2 lesions. However, to improve survival without colostomy with good anal sphincter function, chemoradiotherapy should be preferred for tumors > or =2 cm in length and for locally advanced tumors.