Delineating brachial plexus, cochlea, pharyngeal constrictor muscles and optic chiasm in head and neck radiotherapy: a CT-based model atlas.

BACKGROUND AND PURPOSE: Sparing of the organs at risk is one of the primary end-points of radiotherapy. The effects of organ-at-risk delineation on the dosimetric parameters can be critical and can influence treatment planning and outcomes. The aim of our study was to provide anatomical boundaries for the identification and delineation of the following critical organs at risk in the head and neck district: brachial plexus, cochlea, pharyngeal constrictor muscles and optic chiasm. PATIENTS AND METHODS: One patient was initially selected to elaborate our atlas. This patient was subjected to a planning computed tomography of the brain and head and neck district; axial images of 3-mm thickness at 3-mm intervals were obtained. In the same set-up a magnetic resonance imaging study was also performed. The obtained images were fused based on anatomical landmarks and used by a radiation oncologist, supported by a neuroradiologist, to provide anatomo-radiological limits for the identification of the brachial plexus, cochlea, pharyngeal constrictor muscles and optic chiasm. These limits were further verified on three consecutive patients. RESULTS: A computed tomography-based atlas was developed with definition of cranial, caudal, medial, lateral, anterior and posterior limits for each organ considered. CONCLUSIONS: This study allows improvement of definitions of anatomic boundaries for the brachial plexus, cochlea, pharyngeal constrictor muscles and optic chiasm. Our multidisciplinary experience led to the production of an institutional reference tool that could represent a useful aid for radiation oncologists in clinical practice.

Parotid glands in whole-brain radiotherapy: 2D versus 3D technique for no sparing or sparing.

PURPOSE: Whole-brain radiotherapy is performed as standard therapy in patients with multiple brain metastases and in patients with more favourable prognosis such as lymphoma and small-cell lung carcinoma in the prophylactic setting. Because of the prognosis and the total prescribed dose, the parotid glands are not usually regarded as an organ at risk in whole-brain radiotherapy. Long-term survival can be expected in some of these patients and late toxicity can be observed, becoming essential to evaluate organs at risk, particularly the parotid glands even in metastatic patients. We compared the 2D with 3D technique to evaluate parotid glands involvement and received dose, and coverage of the clinical target volume. MATERIALS AND METHODS: Seven patients were considered. The prescribed dose was 30 Gy in ten fractions. On the same day and with the same set-up, all the treatment planning were performed using a 2D and 3D technique. A treatment plan was performed following same technical characteristics as the 2D technique. The parotid glands and whole brain were delineated. Dose-volume statistics were analysed. RESULTS: Dose-volume histograms of the parotid glands showed that 2/7 patients (28 %) received a mean dose >20 Gy. We found a lack of coverage of the clinical target volume in 6/7 patients. CONCLUSIONS: Planning whole-brain radiotherapy with only the 2D technique involves a risk of including parotid glands in the field and not covering the clinical target volume. The 3D technique should be systematically performed and the parotid glands should be regarded as an organ at risk in whole-brain radiotherapy.

Developing a decision-making model based on an interdisciplinary oncological care group for the management of colorectal cancer.

AIM: To report our experience on implementation and preliminary results of a decision-making model based on the recommendations of an Interdisciplinary Oncological Care Group developed for the management of colorectal cancer. PATIENTS AND METHODS: The multidisciplinary team identified a reference guideline using appraisal of guidelines for research and evaluation (AGREE) tool based on a sequential assessment of the guideline quality. Thereafter, internal guidelines with diagnostic and therapeutic management for early, locally advanced and metastatic colonic and rectal cancer were drafted; organizational aspects, responsibility matrices, protocol actions for each area of specialty involved and indicators for performing audits were also defined. RESULTS: The National Institute for Health and Care Excellence (NICE) UK guideline was the reference for drafting the internal guideline document; from February to November 2013, 125 patients with colorectal cancer were discussed by and taken under the care of the Interdisciplinary Oncological Care Group. The first audit performed in December 2013 revealed optimal adherence to the internal guideline, mainly in terms of uniformity and accuracy of perioperative staging, coordination and timing of multi-modal therapies. To date, all patients under observation are within the diagnostic and therapeutic course, no patient came out from the multidisciplinary "path" and only in 14% of cases have the first recommendations proposed been changed. The selected indicators appear effective and reliable, while at the moment, it is not yet possible to assess the impact of the multidisciplinary team on clinical outcome. CONCLUSION: Although having a short observation period, our model seems capable of determining optimal uniformity of diagnostic and therapeutic management, to a high degree of patient satisfaction. A longer observation period is necessary in order to confirm these observations and for assessing the impact on clinical outcome.

Human epidermal growth factor receptor-2 positivity predicts locoregional recurrence in patients with T1-T2 breast cancer.

AIM: To determine the impact of biological subtypes defined by hormonal receptors and human epidermal growth factor receptor-2 status on risk of recurrence in women with invasive breast cancer treated with breast-conserving therapy. PATIENTS AND METHODS: Between 2001-2005, we observed 590 women with invasive breast cancer. They underwent conservative surgery, adjuvant radiotherapy and hormonotherapy or chemotherapy. None received adjuvant trastuzumab. The Kaplan-Meier method was applied to calculate for the 36-month and 60-month rates of locoregional recurrence-free survival and overall survival. RESULTS: The overall 36- and 60-month actuarial Kaplan-Meier survival rates were 98.5% and 97.7%, respectively; the locoregional recurrence-free survival rates were 95.2% and 91.2%, respectively. Locoregional recurrence rate was significantly greater in patients with human epidermal growth factor receptor-2 (15.2% vs. 5.3%, p<0.001). CONCLUSIONS: Patients with hormone receptor-negative or human epidermal growth factor receptor-2-positive T1-T2 breast cancer seem to have a greater risk of disease recurrence.

Postoperative 5-FU based radiochemotherapy in rectal cancer: retrospective long term results and prognostic factors of a pooled analysis on 1,338 patients.

AIM: To evaluate survival outcomes of patients in pStage II-III rectal cancer treated with adjuvant 5-fluorouracil-based radiochemotherapy and to retrospectively analyze the impact of prognostic variables on local control, metastasis-free survival and cause-specific survival. PATIENTS AND METHODS: A total of 1,338 patients, treated between 1985-2005 for locally advanced rectal cancer, who underwent surgery and postoperative 5-fluorouracil-based chemoradiation, were selected. RESULTS: The actuarial 5- and 10-year outcomes were: local control 87.0%-84.1%, disease-free survival 61.6%-52.1%, metastasis-free survival 72.0%-67.2%, cause-specific survival 70.4%-57.5%, and overall survival 63.8%-53.4%. Better outcomes were observed in patients with IIA, IIIA stage. Multivariate analyses showed that variables significantly affecting metastasis-free survival were pT4 and pN2, while for cancer-specific survival those variables were age >65 years, pT4, pN1, pN2, distal tumors and number of lymph nodes removed ≤ 12. CONCLUSION: This study confirmed that among stage II-III rectal cancer patients there are subgroups of patients with different clinical outcomes.

Prognostic impact of hemoglobin level and other factors in patients with high-grade gliomas treated with postoperative radiochemotherapy and sequential chemotherapy based on temozolomide: a 10-year experience at a single institution.

BACKGROUND AND PURPOSE: To evaluate the influence of serum hemoglobin level prior to radiotherapy and other prognostic factors on survival in patients with high-grade gliomas. MATERIAL AND METHODS: From 2001-2010, we retrospectively evaluated a total of 48 patients with malignant glioma treated with surgery and postoperative radiochemotherapy with temozolomide. A total of 37 of 48 patients received sequential temozolomide. Hemoglobin levels were assayed before radiotherapy in all patients. The Kaplan-Meier method was applied to estimate the overall survival, while the log-rank test was applied to evaluate the differences on survival probability between prognostic subgroups. RESULTS: Results were assessed in 43 patients. The median overall survival time was 18 months (95% confidence interval: 12-40 months). The 1- and 2-year survival rates were 62.2% and 36.3%, respectively. The prognostic factors analyzed were gender, age, extent of surgery, performance status before and after radiotherapy, sequential chemotherapy, hemoglobin level, and methylation of the O-6-methylguanine-DNA methyltransferase gene (MGMT). In univariate analysis, the variables significantly related to survival were performance status before and after radiotherapy, sequential chemotherapy, and hemoglobin level. The median overall survival in patients with a hemoglobin level ≤ 12 g/dl was 12 months and 23 months in patients with a hemoglobin level > 12 g/dl. The 1- and 2-year survival rates were 46.7% and 20.0%, respectively, for patients with a hemoglobin level ≤ 12 mg/dl and 69.6% and 45.7%, respectively, for patients with a hemoglobin level > 12 g/dl. CONCLUSION: Our results confirm the impact of well-known prognostic factors on survival. In this research, it was found that a low hemoglobin level before radiotherapy can adversely influence the prognosis of patients with malignant gliomas.

Interobserver variability of clinical target volume delineation in supra-diaphragmatic Hodgkin's disease: a multi-institutional experience.

BACKGROUND: To determine interobserver variability in clinical target volume (CTV) of supra-diaphragmatic Hodgkin's lymphoma. MATERIALS AND METHODS: At the 2008 AIRO (Italian Society of Radiation Oncology) Meeting, the Radiation Oncology Department of Chieti proposed a multi-institutional contouring dummy-run of two cases of early stage supra-diaphragmatic Hodgkin's lymphoma after chemotherapy. Clinical history, diagnostics, and planning CT imaging were available on Chieti's radiotherapy website (www.radioterapia.unich.it). Participating centers were requested to delineate the CTV and submit it to the coordinating center. To quantify interobserver variability of CTV delineations, the total volume, craniocaudal, laterolateral, and anteroposterior diameters were calculated. RESULTS: A total of 18 institutions for case A and 15 institutions for case B submitted the targets. Case A presented significant variability in total volume (range: 74.1-1,157.1 cc), craniocaudal (range: 6.5-22.5 cm; median: 16.25 cm), anteroposterior (range: 5.04-14.82 cm; median: 10.28 cm), and laterolateral diameters (range: 8.23-22.88 cm; median: 15.5 cm). Mean CTV was 464.8 cc (standard deviation: 280.5 cc). Case B presented significant variability in total volume (range: 341.8-1,662 cc), cranio-caudal (range: 8.0-28.5 cm; median: 23 cm), anteroposterior (range: 7.9-1.8 cm; median: 11.1 cm), and laterolateral diameters (range: 12.9-24.0 cm; median: 18.8 cm). Mean CTV was 926.0 cc (standard deviation: 445.7 cc). CONCLUSION: This significant variability confirms the need to apply specific guidelines to improve contouring uniformity in Hodgkin's lymphoma.

Retrospective long-term results and prognostic factors of postoperative treatment for UICC stages II and III rectal cancer.

AIMS: To retrospectively evaluate 5-year local control, disease-free survival, cancer-specific survival and overall survival rates in patients with UICC stages II and III rectal cancer treated with adjuvant therapy and especially to analyze the impact of some prognostic factors on clinical outcome at univariate and multivariate analyses. METHODS AND MATERIALS: We retrospectively reviewed 306 patients treated with postoperative 5-fluorouracil-based chemoradiation (278 patients) or radiotherapy alone (28 patients) after curative surgery. The following prognostic factors were considered at univariate and multivariate analyses: age, sex, tumor location, surgery procedure, pathological stage, histology, tumor grade, surgical margins and radiotherapy technique. RESULTS: The 5-year actuarial rates for local control, disease-free survival, cancer-specific survival and overall survival were respectively 89.7%, 59.7%, 68.6% and 61.4% for the 278 patients (91%) treated with postoperative chemoradiation. Univariate analysis showed that abdominal-perineal resection impacted disease-free survival and that the T4 variable had an impact on cancer-specific survival and disease-free survival. Instead, age > or = 70, N2, IIIB (p T3 p N1) and IIIC (p T3 p N2) stage impacted cancer-specific survival, disease-free survival and rate of distant metastases. Multivariate analysis showed as significant variables age > or = 70 years, pN1 and pN2 and extraperitoneal tumor location. CONCLUSIONS: Our retrospective study showed a good 5-year local control. Factors such as individual pT4, pN1, pN2, age > or = 70 years, abdominal-perineal resection, stages IIIB-IIIC versus II-IIIA and extraperitoneal tumor location negatively influenced disease-free survival, distant metastases and cancer-specific survival. Differences exist between stages II and III rectal cancer and treatment modulation and intensification are required in order to offer the most appropriate and effective adjuvant treatment and to improve survival of rectal cancer patients.

The effect of delaying adjuvant radiation treatment after conservative surgery for early breast cancer.

We examined the effect of delaying radiation treatment after conservative surgery on the risk of breast cancer local recurrence (LR). From January 1997 to December 2001, 969 women with early-stage breast cancer were treated at the Radiation Oncology Department in Chieti. We analyzed 802 of them who underwent conservative surgery followed by whole-breast radiotherapy. The patients were divided into two groups: women who did not receive chemotherapy and women who received chemotherapy. The time intervals from surgery to breast irradiation used for the analysis were <16 or more weeks for no-chemotherapy-treated women, and <25 and 25 or more weeks for chemotherapy-treated women. The relationship between LR and factors such as age, tumor size, margin status, and surgery-radiotherapy time interval was evaluated. The 8-year LR risk was estimated using the Kaplan-Meier method. LR was observed in 33 (4.1%) of the 802 patients. The overall 8-year LR risk was 6.5% (+/-1.51). In the no-chemotherapy group, the risk of LR was associated with a younger age and a positive margin status. In the chemotherapy group LR was associated with a younger age and a tumor size >3 cm. Surgery-radiotherapy interval was not associated with LR in both groups of patients. Delay in the start of radiotherapy does not increase the risk of LR in patients with early breast cancer treated or not treated with chemotherapy.

Predictors of local recurrence after conservative surgery and whole-breast irradiation.

PURPOSE: To identify independent factors associated with increased risk of local recurrence (LR) in patients with breast cancer treated with conservative surgery and radiotherapy with or without systemic therapy. METHODS AND MATERIALS: Between January 1997 and December 2001, 969 women were treated at the Radiation Oncology Department in Chieti. We retrospectively analyzed 802 of them who were treated with conservative surgery and whole breast irradiation with or without systemic therapy. Tangential fields delivering 50 Gy to the whole breast were used and a boost was added for a total dose of 60 Gy. chi(2)-test or Fisher's exact test were used to identify independent significant factors that are predictive for LR. Kaplan-Meier method was used to calculate the 8-year rates of recurrence according to age, histologic findings, tumor size, number of positive nodes, margin status, receptor status and systemic therapy use: log-rank test was used to compare these curves. Cox proportional hazard model was used to obtain hazard ratios and 95% CI of LR for each covariate. RESULTS: Median follow-up time was 63.1 months. LR occurred in 33 (4.1%) of 802 patients. Percentage of LR was greater in <50 year-olds compared with 50-64 year-olds and > or =65 year-olds (9.8% versus 4.1 and 2.0%, respectively). LR was 18.8% in women with a tumor size >3 cm versus 3.5, 4.0, 5.5% in women with a tumor size of 0.1-1, 1.1-2, 2.1-3 cm, respectively. The 8-year LR rate calculated with Kaplan-Meier method was 6.54+/-1.51. Multivariate Cox regression analysis showed that independent significant factors that are predictive for LR were: age <50, tumor size >3 cm, positive margin or unknown status, and hormonal therapy alone versus chemotherapy or combined therapy. CONCLUSIONS: Age and tumor size were the most important and statistically significant factors that correlated independently with higher rates of LR. Women <50 years old and with a tumor size >3 cm had a higher risk of LR. Also margin status and systemic therapy could influence LR risk.

Transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma in cirrhotics: functional hepatic reserve and survival.

BACKGROUND/AIMS: Transarterial chemoembolization is widely used for palliative treatment of hepatocellular carcinoma, but patient's characteristics associated with maximal benefit are still undefined. METHODOLOGY: In 81 cirrhotic patients with unresectable hepatocellular carcinoma, who underwent transarterial chemoembolization, variables correlated with survival were studied. In 46/81, the antipyrine metabolism test has been performed before and 72 hours after first transarterial chemoembolization. RESULTS: Mean overall survival of whole population was 22 months. One-, two-, and three-year survival rates were respectively 85%, 38.6%, and 18.1%. Better survival was observed in those patients who received more than one treatment (p = 0.016), while no relationship was found with treatment response, drug used, or number of lobes involved. Univariate analysis of the subgroup with antipyrine pharmacokinetic data revealed a significant relation between survival and baseline albumin (p = 0.039), total cholesterol (p = 0.036), AST (p = 0.017), log of total bilirubin (p = 0.017), and Child-Pugh class (p = 0.029), but not with parameters of antipyrine metabolism. Antipyrine metabolism was not significantly modified by transarterial chemoembolization in the subgroup tested before and after the first treatment. Using Cox regression analysis and selecting AST and log of total bilirubin, a prognostic index was defined: prognostic index 0.006 (AST-83.044) + 0.638 [log of total bilirubin-0.1175]. One-, two-, and three-year survival rates were respectively 92%, 59.2%, and 29.6% for the patient group with prognostic index < 0, and 76%, 14.3%, and 4.8% for the group with prognostic index > 0 (p < 0.01). CONCLUSIONS: Transarterial chemoembolization is a safe procedure and appears beneficial for those patients with a good functional hepatic reserve. The antipyrine metabolism test does not provide any additional prognostic information.

Primary malignant lymphoma of the saphenous vein.

We herein present a case of primary malignant lymphoma of the saphenous vein. A 72-year-old man suffered from tumor and pain of the anteromedial aspect of the left upper thigh. Local thigh ultrasound scanning and computed tomography revealed a mass within the superior third of the internal saphenous vein. The patient underwent surgical exploration and removal of the saphenous vein between the groin and the upper third of the leg. The resected vessel was surrounded and infiltrated by a whitish, rubbery tissue all along its course. The histologic findings were consistent with high-grade, diffuse, large-cell lymphoma of peripheral B lymphocyte origin, primarily arising in the saphenous vein. Antiactin monoclonal antibodies depicted the venous vascular wall infiltrated by tumor cells, confirming the lymphomatous localization within the saphenous vein. The patient is now alive and free of tumor 10 months after the operation.