Laura Marucci

Treatment and outcome of advanced external auditory canal and middle ear squamous cell carcinoma.

This is a retrospective study to evaluate the outcomes and complications of combined treatment, surgery with or without adjunctive intraoperative radiotherapy, of locally advanced temporal bone squamous cell carcinoma. A series of 17 patients with locally advanced squamous cell carcinoma of the temporal bone were treated between September 2002 and February 2007. Eleven patients had primary tumors, and 6 patients had recurrences. According to the University of Pittsburgh staging system, 5 patients were stage II (T2 N0), 6 patients were stage III (5, T3 N0 and 1, T1 N1), and 6 patients were stage IV (5, T3 N2b and 1, T4 N0). All patients underwent lateral temporal bone resection and pedicle flap reconstruction. Eight patients received intraoperative and postoperative radiotherapies, 4 patients underwent postoperative radiation alone, whereas 5 patients did not receive any adjunctive treatment. Median follow-up was 29.5 months. No major complications were observed. No patients were found to have residual gross tumor. Disease-free survival was 73.3%, and overall survival was 75.6%. Radical external auditory canal and/or middle ear canal resection is of utmost importance to obtain a good surgical outcome. Postoperative radiotherapy is necessary to obtain good local control; no major adverse effects were observed in the intraoperative radiotherapy patients. The incidence of major complication is minimal after pedicle flap reconstruction.

Early radiation-induced changes evaluated by intravoxel incoherent motion in the major salivary glands

To investigate the potential of intravoxel incoherent motion (IVIM) MRI for early evaluation of irradiated major salivary glands.

Analysis of Salivary Flow and Dose-Volume Modeling of Complication Incidence in Patients With Head-and-Neck Cancer Receiving Intensity-Modulated Radiotherapy

PURPOSE To investigate dose-volume effects of salivary flow and the functional recovery over time, using salivary function data and different models of normal tissue complication probability (NTCP). METHODS AND MATERIALS A total of 59 patients with head-and-neck cancer treated with intensity-modulated radiotherapy (IMRT) were analyzed in the present study. The toxicity was evaluated using the Radiation Therapy Oncology Group (RTOG) scale and salivary flows, both unstimulated (USF) and stimulated (SSF). The assessments were done before radiotherapy (RT) and at 3, 6, 12, 18, and 24 months after RT. Grade 3 toxicity was the primary endpoint. Analyses of toxicity incidence at 3, 6, and 12 months after RT were performed by both the Lyman-Kutcher-Burman (LKB) and relative seriality (S) models. RESULTS A significant correlation was found between the incidence of Grade 3 toxicity and the incidence of patients with a reduction in SSF to <25% of the pre-RT value. Better correlations resulted between the RTOG toxicity score and the dosimetric parameters, compared with USF/SSF. The TD(50), assessed by the LKB model, was 21.4, 27.8, and 41.6 Gy at 3, 6, and 12 months after RT, respectively. The TD(50), assessed by the S model, was 20.0, 26.3, and 40.0 Gy at 3, 6, and 12 months after RT, respectively. CONCLUSION Recovery of salivary gland function vs. time after RT took place mostly within 1 year after RT. The RTOG Grade 3 was a reliable score to perform the NTCP modeling. The choice of NTCP model had no influence on the accuracy of predictions.

Uveal Melanoma Recurrence After Fractionated Proton Beam Therapy: Comparison of Survival in Patients Treated With Reirradiation or With Enucleation

PURPOSE To retrospectively compare survival in recurrent uveal melanoma, between patients treated by enucleation or by a second course of fractionated proton beam therapy (PBT). METHODS AND MATERIALS Tumor recurrence was documented in 73 patients treated with PBT for uveal melanoma. Of the patients, 31 received a second course of PBT and 42 underwent enucleation. The mean patient age was 56 and 61 years for those undergoing enucleation and those undergoing reirradiation, respectively. Both primary and recurrent tumors were larger in patients undergoing enucleation. Tumor location and the presence or absence of ciliary body involvement did not differ significantly between the groups. The median follow-up after enucleation and after re-treatment was 79 and 59 months, respectively. Cumulative rates of outcomes and differences in rates between the reirradiated and enucleation groups were calculated by the Cox proportional hazards model and the log-rank test, respectively. RESULTS The median survival duration in the enucleated and reirradiated groups was 42 and 90 months, respectively. The median time free of metastases was 38 months in enucleated patients and 97 months in reirradiated patients. At 5 years after enucleation and after reirradiation, the probability of overall survival was 36% and 63%, respectively (p=0.040, log-rank test); the probability of freedom from metastases was 31% and 66%, respectively (p=0.028, log-rank test). These differences persisted after adjustment for recurrent tumor largest diameter and volume at the time of reirradiation or enucleation. CONCLUSIONS This retrospective analysis suggests that survival in reirradiated patients is not compromised by administration of a second course of PBT for recurrent uveal melanoma.

Accelerated hypofractionated radiotherapy as adjuvant regimen after conserving surgery for early breast cancer: interim report of toxicity after a minimum follow up of 3 years

BackgroundAccelerated hypofractionation is an attractive approach for adjuvant whole breast radiotherapy. In this study we evaluated the adverse effects at least 3 years post an accelerated hypofractionated whole breast radiotherapy schedule.MethodsFrom October 2004 to March 2006, 39 consecutive patients aged over 18 years with pTis, pT1-2, pN0-1 breast adenocarcinoma who underwent conservative surgery were treated with an adjuvant accelerated hypofractionated radiotherapy schedule consisting of 34 Gy in 10 daily fractions over 2 weeks to the whole breast, followed after 1 week by an electron boost dose of 8 Gy in a single fraction to the tumour bed. Skin and lung radiation toxicity was evaluated daily during therapy, once a week for one month after radiotherapy completion, every 3 months for the first year and from then on every six months. In particular lung toxicity was investigated in terms of CT density evaluation, pulmonary functional tests, and clinical and radiological scoring. Paired t-test, Chi-square test and non-parametric Wilcoxon test were performed.ResultsAfter a median follow-up of 43 months (range 36-52 months), all the patients are alive and disease-free. None of the patients showed any clinical signs of lung toxicity, no CT-lung toxicity was denoted by radiologist on CT lung images acquired about 1 year post-radiotherapy, no variation of pulmonary density evaluated in terms of normalised Hounsfield numbers was evident. Barely palpable increased density of the treated breast was noted in 9 out of 39 patients (in 2 patients this toxicity was limited to the boost area) and teleangectasia (<1/cm2) limited to the boost area was evident in 2 out of 39 patients. The compliance with the treatment was excellent (100%).ConclusionThe radiotherapy schedule investigated in this study (i.e 34 Gy in 3.4 Gy/fr plus boost dose of 8 Gy in single fraction) is a feasible and safe treatment and does not lead to adjunctive acute and late toxicities. A longer follow up is necessary to confirm these favourable results.

A Novel Dose Constraint to Reduce Xerostomia in Head-and-Neck Cancer Patients Treated With Intensity-Modulated Radiotherapy

PURPOSE To investigate the predictors of incidence and duration of xerostomia (XT) based on parotid glands (PG), submandibular glands (SMG), and both glands taken as a whole organ (TG) in head-and-neck cancer patients treated with intensity-modulated radiotherapy. METHODS AND MATERIALS A prospective study was initiated in May 2003. Sixty-three head-and-neck patients (44 with nasopharynx cancer) were included in the analysis. Using the dose-volume histogram the PG, SMG, and TG mean doses were calculated. Unstimulated and stimulated salivary flow were measured and XT-related questionnaires were compiled before and at 3, 6, 12, 18, and 24 months after radiotherapy. Salivary gland toxicity was evaluated using the Radiation Therapy Oncology Group scale, and Grade >or=3 toxicity was used as the endpoint. The XT incidence was investigated according to descriptive statistics and univariate and multivariate analysis. The Bonferroni method was used for multiple comparison adjustment. RESULTS After a reduced flow at 3 months after radiotherapy, recovery of salivary flow was observed over time. Primary site and salivary gland mean doses and volumes were identified in univariate analysis as prognostic factors. Multivariate analysis confirmed that TG mean dose (p = 0.00066) and pretreatment stimulated salivary flow (p = 0.00420) are independent factors for predicting XT. CONCLUSION The TG mean dose correlates with XT as assessed by Radiation Therapy Oncology Group criteria, salivary output, and XT-related questionnaires. Our results suggest that TG mean dose is a candidate dose constraint for reducing XT, requiring considerably more validation in non-nasopharyngeal cancer patients.

A new model for predicting acute mucosal toxicity in head-and-neck cancer patients undergoing radiotherapy with altered schedules.

PURPOSE One of the worst radiation-induced acute effects in treating head-and-neck (HN) cancer is grade 3 or higher acute (oral and pharyngeal) mucosal toxicity (AMT), caused by the killing/depletion of mucosa cells. Here we aim to testing a predictive model of the AMT in HN cancer patients receiving different radiotherapy schedules. METHODS AND MATERIALS Various radiotherapeutic schedules have been reviewed and classified as tolerable or intolerable based on AMT severity. A modified normal tissue complication probability (NTCP) model has been investigated to describe AMT data in radiotherapy regimens, both conventional and altered in dose and overall treatment time (OTT). We tested the hypothesis that such a model could also be applied to identify intolerable treatment and to predict AMT. This AMT NTCP model has been compared with other published predictive models to identify schedules that are either tolerable or intolerable. The area under the curve (AUC) was calculated for all models, assuming treatment tolerance as the gold standard. The correlation between AMT and the predicted toxicity rate was assessed by a Pearson correlation test. RESULTS The AMT NTCP model was able to distinguish between acceptable and intolerable schedules among the data available for the study (AUC = 0.84, 95% confidence interval = 0.75-0.92). In the equivalent dose at 2 Gy/fraction (EQD2) vs OTT space, the proposed model shows a trend similar to that of models proposed by other authors, but was superior in detecting some intolerable schedules. Moreover, it was able to predict the incidence of ≥G3 AMT. CONCLUSION The proposed model is able to predict ≥G3 AMT after HN cancer radiotherapy, and could be useful for designing altered/hypofractionated schedules to reduce the incidence of AMT.

Influence of intensity‐modulated radiation therapy technique on xerostomia and related quality of life in patients treated with intensity‐modulated radiation therapy for nasopharyngeal cancer

The purpose of this study was to compare 5‐field and 7‐field intensity‐modulated radiation therapy (IMRT) techniques in terms of xerostomia and related quality of life in patients with nasopharyngeal cancer.

Planned neck dissection after chemoradiotherapy in advanced oropharyngeal squamous cell cancer: the role of US, MRI and FDG-PET/TC scans to assess residual neck disease.

OBJECTIVE To investigate the ability of neck ultrasounds (US), magnetic resonance imaging (MRI) and positron emission tomography (FDG-PET/TC) in detecting residual nodal disease after chemoradiotherapy in patients with advanced oropharyngeal squamous cell carcinoma (OPSCC). METHODS From 2006 to 2009, 36 consecutive patients affected by OPSCC with bulky nodal disease (>3 cm), treated with primary concurrent chemoradiotherapy, were enrolled prospectively. Nodal response to treatment was assessed by using US, MRI and FDG-PET/CT. Planned neck dissection (ND) was performed in all the patients, and the histopathological node status was compared to the imaging findings in order to establish sensitivity, specificity, accuracy and predictive values of each technique. RESULTS Metastatic disease was assessed in 18/37 (48.6%) hemi-necks, always localized in levels II-IV. US showed greater sensitivity (77.8%) and, combined with FDG-PET/TC, produced the highest negative predictive value (93.3%). US, MRI and FDG-PET/TC scans showed the highest specificity (100%), accuracy (93.8%) and positive predictive values (100%). CONCLUSIONS In the presence of advanced OPSCC with bulky nodal disease, US combined with FDG-PET/TC could be a reliable and cost-effective strategy to identify patients with complete nodal response to chemoradiotherapy that might not require post-treatment ND but only observation. When residual disease in the neck was detected, selective ND was recommended.

Double‐blind randomized phase III study comparing a mixture of natural agents versus placebo in the prevention of acute mucositis during chemoradiotherapy for head and neck cancer

There is no widely accepted intervention in the prevention of acute mucositis during chemoradiotherapy for head and neck carcinoma. In the present double‐blind study, we tested 4 natural agents, propolis, aloe vera, calendula, and chamomile versus placebo.