Stereotactic radiotherapy for bone oligometastases.

About 60-90% of cancer patients are estimated to develop bone metastases, particularly in the spine. Bone scintigraphy, computed tomography (CT ) and magnetic resonance imaging (MRI ) are currently used to assess metastatic bone disease; positron emission tomography/computed tomography (PET-CT ) has become more widespread in clinical practice because of its high sensitivity and specificity with about 95% diagnostic accuracy. The most common and well-known radiotracer is 18F-fluorodeoxyglucose (18FDG); several other PET-radiotracers are currently under investigation for different solid tumors, such as 11C or 18FDG-choline and prostate specific membrane antigen (PSMA)-PET/CT for prostate cancer. In treatment planning, standard and investigational imaging modalities should be registered with the planning CT so as to best define the bone target volume. For target volume delineation of spine metastases, the International Spine Radiosurgery Consortium (ISRC ) of North American experts provided consensus guidelines. Single fraction stereotactic radiotherapy (SRT ) doses ranged from 12 to 24 Gy; fractionated SRT administered 21-27 Gy in 3 fractions or 20-35 Gy in 5 fractions. After spine SRT, less than 5% of patients experienced grade ≥ 3 acute toxicity. Late toxicity included the extremely rare radiation-induced myelopathy and a 14% risk of de novo vertebral compression fractures.

Analysis of skin dose distribution for the prediction of severe radiation dermatitis in head and neck squamous cell carcinoma patients treated with concurrent chemo-radiotherapy.

BACKGROUND: We investigated whether the pattern of intensity-modulated radiotherapy (IMRT) dose distribution to the skin can be correlated with the development of G3/G4 radiation dermatitis (RD). METHODS: A frequency-matched cohort analysis was perfomed on patients treated with IMRT and concurrent cisplatin or cetuximab. Risk ratios were obtained by fitting Poisson regression models. RESULTS: The incidence of G3/G4 RD was 41.1% in 90 patients included (50% vs 36.6% in the cetuximab and cisplatin cohorts, respectively). In multivariate analysis, PS ≥ 1 and weight loss at RT completion >10 kg were the only factors that retained significance. The best dosimetric predictive accuracy was provided by 19.9 cc and 5.8 cc of skin ring 2 mm V50 and V60, respectively (AUC: 0.61 for both). CONCLUSION: Along with clinical factors, the pattern of dose distribution to a ring structure localized 2 mm below the patient's surface may help predict the development of severe RD.

Xerostomia Quality of Life Scale (XeQoLS) questionnaire: validation of Italian version in head and neck cancer patients.

AIM: To translate the Xerostomia Quality-of-Life Scale (XeQoLS) into Italian language (XeQoLS-IT). Xerostomia is the most relevant acute and late toxicity in patients with head and neck cancer treated with radiotherapy (RT). Patient-reported outcome (PRO) instruments are subjective report on patient perception of health status. The XeQoLS consists of 15 items and measures the impact of salivary gland dysfunction and xerostomia on the four major domains of oral health-related QoL. METHODS: The XeQoLS-IT was created through a linguistic validation multi-step process: forward translation (TF), backward translation (TB) and administration of the questionnaire to 35 Italian patients with head and neck cancer. Translation was independently carried out by two radiation oncologists who were Italian native speakers. The two versions were compared and adapted to obtain a reconciled version, version 1 (V1). V1 was translated back into English by an Italian pro skilled in teaching English. After review of discrepancies and choice of the most appropriate wording for clarity and similarity to the original, version 2 (V2) was reached by consensus. To evaluate version 2, patients completed the XeQoLS-IT questionnaire and also underwent a cognitive debriefing. RESULTS: The questionnaire was considered simple by the patients. The clarity of the instructions and the easiness to answer questions had a mean value of 4.5 (± 0.71) on a scale from 1 to 5. CONCLUSION: A valid multi-step process led to the creation of the final version of the XeQoLS-IT, a suitable instrument for the perception of xerostomia in patients treated with RT.

Late toxicity, evolving radiotherapy techniques, and quality of life in nasopharyngeal carcinoma.

PURPOSE: To analyze quality of life (QoL) and functional state (FS) by patient-reported outcome (PRO) questionnaires (FACT-G, FACT-NP, PSS-HN, XeQOLS, and EQ-5D-3L) in long-term survivors nasopharyngeal carcinoma (NPC) treated with conventional radiotherapy (RT) and intensity modulated radiotherapy (IMRT). METHODS: 25 patients answered to five questionnaires about QoL and FS. All patients were assessed also for late toxicity. RESULTS: Functional Assessment of Cancer Therapy-General (FACT-G) and Performance Status Scale Head and Neck (PSS-HN) scores were significantly elevated (better QoL) in age <50 years (p = 0.03). PSS-HN score was higher in IMRT group. The observed xerostomia was lower in the IMRT group and in patients who received conventional RT had worse QoL according to XeQOLS (University of Michigan Xerostomia-Related Quality of Life Scale) score questionnaire. Lower PSS-HN score and higher XeQOLS score were significantly related with the late xerostomia (p = 0.009 and 0.002, respectively). CONCLUSIONS: Our preliminary data suggest that age, older techniques, xerostomia, and hearing loss are negative predictors of QoL.

Advantage of deep inspiration breath hold in left-sided breast cancer patients treated with 3D conformal radiotherapy.

PURPOSE: To compare 3D-conformal radiotherapy (3D-CRT) treatment plans based on free-breathing (FB) and deep inspiration breath hold (DIBH) and investigated whether DIBH technique enables a decrease of cardiac left anterior descending coronary artery (LADCA) and lungs dose with respect to the FB. METHODS: Twenty-three left-sided breast cancer patients referred for breast radiotherapy were included. The planning target volume (PTV) encompassed the breast and organs at risk including heart, LADCA, lungs, and contralateral breast, which were contoured in FB and DIBH CT scans. Dose to PTV was 50 Gy in 25 fractions. Two treatment plans were generated for each patient: FB-3D-CRT and DIBH-3D-CRT. Dosimetry parameters were obtained from dose volume histograms. Data were compared using the paired-sample Wilcoxon signed rank test. RESULTS: For heart, LADCA, and left lung, a significant dose reduction was found using DIBH technique. By using DIBH, an average reduction of 25% was observed in LADCA for the volume receiving 20 Gy and of 48% considering the mean heart dose. CONCLUSIONS: The DIBH technique results in a significant decrease of dose to the heart, LADCA, and left lung compared to FB.

Subgroup Analysis According to Human Papillomavirus Status and Tumor Site of a Randomized Phase II Trial Comparing Cetuximab and Cisplatin Combined With Radiation Therapy for Locally Advanced Head and Neck Cancer.

PURPOSE: We report a subgroup analysis primarily focused on human papillomavirus (HPV)-related oropharyngeal cancer (OPC) from the Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer (CTXMAB+RT; ClinicalTrials.gov identifier NCT01216020) trial comparing radiation therapy with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced head and neck cancer. METHODS AND MATERIALS: The data from all the patients in the CTXMAB+RT trial were reviewed and separately analyzed in 3 groups: p16-positive OPC, p16-negative OPC, and all other cancer sites. The endpoints of interest were locoregional control (LC), metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS). Severe and fatal infectious complications were also reanalyzed to more thoroughly investigate the association between CTX treatment and potentially life-threatening reactions. RESULTS: A total of 33 patients had OPC. The HPV status was available for 30 of the 33 patients. Thus, 3 patients treated with CDDP but with unknown HPV status were excluded from the survival analysis. The small number of patients in each group did not allow for significance to be reached for any of the outcomes analyzed. A trend favored the CDDP arm in the p16-positive group for the 2-year LC and OS/CSS rates (100% vs 72.9% and 100% vs 77.8% for CDDP vs CTX). In this group of patients, the hazard ratio for the treatment arm (CTX vs CDDP) was 4.7 (95% confidence interval [CI] 0.5-40.3) for LC, 3.4 (95% CI 0.4-30.5) for OS, and 2.4 for CSS (95% CI 0.2-23.2). A survival benefit favoring the CDDP arm was not evident in the p16-negative OPC group or for patients with cancer located in other sites. Serious or fatal infectious complications occurred only in the CTX arm. CONCLUSIONS: In patients with p16-positive OPC in the CTXMAB+RT trial, CTX had lower efficacy than CDDP, with possible implications for treatment selection in this clinical setting.

Predictive factors for additional non-sentinel lymph node involvement in breast cancer patients with one positive sentinel node.

AIM: The aim of this study was to identify a subgroup of breast cancer patients in whom it is possible to avoid axillary lymph node dissection (ALND) when the sentinel lymph node (SLN) is positive. METHODS: A series of 292 patients treated with breast-conserving surgery or mastectomy underwent ALND after positive SLN detection. To correlate SLN metastasis with the chances of finding additional metastasis in non-SLNs we evaluated the main clinicopathological characteristics. No patients received adjuvant radiotherapy to the axillary region. RESULTS: Fifty-six patients (35.4%) with positive SLNs for macrometastases (n = 158) had additional metastases upon completion ALND compared with 7 patients (5.2%) with micrometastases in the SLN (n = 132). Cases with a higher number of positive axillary lymph nodes tended to have higher pT stage (p = 0.004). In multivariate analysis, pT was confirmed as an independent predictor of non-SLN metastases (OR = 2.40; 95% CI = 1.16-4.99). No patients with micrometastases in SLN and cancer lt;10 mm had additional positive non-SLNs. CONCLUSIONS: Our results, in agreement with the major published studies, suggest that ALND can be avoided in selected patients without the need for additional treatment to the axillary region.

Radiotherapy timing in the treatment of limited-stage small cell lung cancer: the impact of thoracic and brain irradiation on survival.

AIMS AND BACKGROUND: Small cell lung cancer is an aggressive histologic subtype of lung cancer in which the role of chemotherapy and radiotherapy has been well established in limited-stage disease. We retrospectively reviewed a series of limited-stage small cell lung cancers treated with chemotherapy and thoracic and brain radiotherapy. METHODS AND STUDY DESIGN: A total of 124 patients affected by limited-stage small cell lung cancer has been treated over 10 years in our Institute. Fifty-three patients (42.8%) had concomitant radio-chemotherapy treatment and 71 patients (57.2%) a sequential treatment. Eighty-eight patients (70.9%) underwent an association of a platinum-derived drug (cisplatinum or carboplatinum) and etoposide. Prophylactic cranial irradiation was planned in all patients with histologically proven complete response to primary radio-chemotherapy. RESULTS: With a mean follow-up of 2.2 years, complete response was obtained in 50.8% of cases. We found a significant difference between different radio-chemotherapy association approaches (P = 0.007): percentages of overall survival were respectively 10.0%, 12.9% and 5.6% in early, late concomitant and sequential radio-chemotherapy timing. Cranial prophylaxis did not seem to influence overall survival (P = 0.21) or disease-free survival for local relapse (P = 0.34). CONCLUSIONS: Concomitant radio-chemotherapy is the best approach according to our experience. Our results show a benefit of prophylactic cranial irradiation in distant metastasis-free survival.

Impact of a breathing-control system on target margins and normal-tissue sparing in the treatment of lung cancer: experience at the radiotherapy unit of Florence University.

PURPOSE: In lung cancer, a high radiation dose to the target area correlates with better local control but is frequently counterbalanced by a higher risk of lung toxicity. Several methods exist to coordinate respiratory motion in lung radiotherapy. We aimed to investigate the impact of a breathing-control system on irradiated volumes and dosimetric parameters in three-dimensional conformal radiotherapy (3D-CRT) and stereotactic radiotherapy (SRT) treatments. MATERIALS AND METHODS: Twelve patients were scheduled for radical radiotherapy: five for SRT and seven for 3D-CRT. For each patient, in addition to the free-breathing computed tomography (CT) scan, four additional sets of CT slices were acquired using the Active Breathing Coordinator device (ABC, Elekta Oncology Systems Ltd., UK). RESULTS: The volumes acquired with the ABC device were significantly smaller than the free-breathing volumes [23 % reduction of planning tumour volume (PTV), p = 0.002]. ABC allowed a reduction of all dosimetric parameters [2.28 % reduction of percentage volume of lung treated to a dose of ≥ 20 Gy (V20), p = 0.004; 10 % reduction of mean lung dose (MLD), p = 0.009]. Significant differences were found both in SRT and in 3D-CRT, in peripheral and apical lesions. CONCLUSION: In our experience, ABC has the potential to reduce lung toxicity in the treatment of lung cancer; alternatively, it can allow the prescribed dose to be increased while maintaining the same risk of lung toxicity.

Vinorelbine-based chemo-radiotherapy in non-small cell lung cancer.

AIMS AND BACKGROUND: Concomitant radio-chemotherapy improves survival of patients with locally advanced non-small cell lung cancer, with a better local-regional control. METHODS AND STUDY DESIGN: We report our experience with vinorelbine-based chemotherapy in neoadjuvant and radical settings in 43 patients. Regimens consisted of cisplatin plus vinorelbine in 74.4% patients and carboplatin plus vinorelbine in 14.0%; 11.6% underwent mono-chemotherapy with oral vinorelbine. We estimated the crude probability of death or local recurrence by the Kaplan-Meier method. Cox regression models were used to identify the main significant predictors of death or local recurrence. RESULTS: A significant effect of the response to treatment was shown on both local disease free-survival (P = 0.004) and overall survival (P <0.0001). Patients with progressive disease after primary treatment had a significantly higher risk of further relapse at both univariate (P = 0.046) and multivariate regression analysis (P = 0.014) than patients with a complete response. They also showed a significantly higher risk of death at both univariate (P = 0.0005) and multivariate regression analysis (P <0.0001) than patients with a complete response. The most common toxicity was hematologic and gastroenteric. We recorded grade III/IV leukopenia in 11%, anemia in 6%, and esophagitis in 14% of the patients. CONCLUSIONS: Our experience showed that vinorelbine-based chemotherapy is an effective and safe regimen, in association with a platinum compound and thoracic radiotherapy.