Correlation of [18F] FDG-PET/CT with dosimetry data: recurrence pattern after radiotherapy for head and neck carcinoma.

OBJECTIVE: To analyze the pattern of failure in relation to pre-treatment [18F] FDG-PET/CT uptake in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radio-chemotherapy (RT-CHT). METHODS AND MATERIALS: From 2012 to 2016, 87 HNSCC patients treated with definitive RT-CHT, with intensity modulated radiation therapy with simultaneous integrated boost, underwent pre-treatment [18F] FDG-PET/CT (PETpre), and MRI/CT for radiotherapy (RT) planning purposes. Patients with local recurrence, received [18F] FDG-PET/CT, (PETrec) at the time of the discovery of recurrence. In these patients, the metabolic target volume (MTV), MTVpre and MTVrec were segmented on PET images by means of an adaptive thresholding algorithm. The overlapping volume between MTVpre and MTVrec (MTVpre&rec) was generated and the dose coverage of MTVrec and MTVpre&rec was checked on the planning CT using the D99 and D95 dose metrics. The recurrent volume was defined as: ''In-Field (IF)'', "Marginal recurrence" or ''Out-of-Field (OF)'' if D95 was respectively equal or higher than 95%, D95 was between 95 and 20% or the D95 was less than 20% of prescribed dose. RESULTS: We found 10/87 patients (11.5%) who had recurrence at primary site. Mean MTVpre was 12.2 cc (4.6-28.9 cc), while the mean MTVrec was 4.3 cc (1.1-12.7 cc). Two recurrences resulted 100% inside MTVpre, 4 recurrences were mostly inside (61-91%) and 4 recurrences were marginal to MTVpre (1-33%). At dosimetric analysis, five recurrences (50%) were IF, 4 (40%) marginal and one (10%) OF. The mean D99 of the overlapping volumes MTVpre&rec was 68.1 Gy (66.5-69.2 Gy), considering a prescription dose of 70 Gy to the planning target volume (PTV). CONCLUSION: Our study shows that the recurrence may originate from the volume with the highest FDG-signal. Tumor relapse in the high-dose volume support the hypothesis that an intensification of the dose on these volumes could be further assessed to prevent local relapse.

Skin and lung toxicity in synchronous bilateral breast cancer treated with volumetric-modulated arc radiotherapy: a mono-institutional experience.

PURPOSE: To evaluate acute and late skin/subcutaneous toxicities and radiation-induced lung fibrosis (RILF) in patients treated with adjuvant radiotherapy (RT) for synchronous bilateral breast cancers (SBBC), after conservative surgery. METHODS/PATIENTS: Twenty-five patients were treated with volumetric-modulated arc therapy (VMAT/RapidArc®) on both breasts, and checked clinically for detecting RT toxicities during and after treatment. A high-resolution computed tomography (HRCT) was performed, for detecting RILF during follow-up. RESULTS: We registered acute Grade-1 skin toxicity in 18 patients (72%), while six patients (24%) experienced Grade-2 toxicity. No breath symptoms were reported during and after RT. Late Grade-1 subcutaneous toxicity and late Grade-2 skin toxicity were registered in four patients (16%) and one patient (4%), respectively, at a mean follow-up of 36 months. Grade-1 RILF was detected in six patients (30%). The median volume of fibrosis area was 6.5 cc (range 1.3-21.5 cc). The partial volumes receiving a specified dose (V20, V30, V40, and V50) in patients who developed lung fibrosis were significantly bigger than who did not (p < 0.01). We showed that the mean volume of the tumour boost of patients who developed fibrosis (77.7 cc) was not significantly different from the other patients (90.8 cc) (p = 0.5). CONCLUSION: The clinical impact of this technique is favourable, and this is the first clinical study showing RILF by HRCT in a setting of SBBC. Further study with larger accrual is mandatory.

The spine instability neoplastic score (SINS) in the assessment of response to radiotherapy for bone metastases

Background. Vertebral metastases are often causing pain and spine instability. Radiotherapy is of significant benefit for painful spine metastases but the response can be very variable. The spine instability neoplastic score (SINS) is a recent classification system for diagnosis of spinal instability caused by vertebral metastases. We analysed the degree of pain relief, the need of drug therapy and the imaging features and the SINS before and after radiotherapy. In particular, we investigated the possible correlation of spine instability defined by pre-treatment SINS with pretreatment pain and with response to radiotherapy. Material/methods. This study included 121 patients with spine metastases treated with palliative 3D conformal radiotherapy. Pain “at rest” and “breakthrough pain”, need for drug therapy in terms of "anti-inflammatory", "weak opioid", "strong opioid", imaging studies and SINS were assessed before and after radiotherapy. Statistical analysis was performed by the correlation coefficient of Spearman and Kruskal-Wallis test. Results. Pain relief after radiotherapy was observed in 50.4 and 57.8% of patients in terms of pain at rest and breakthrough pain, respectively. The correlation between pain before radiotherapy and SINS was not statistically significant for both pain at rest (p = 0.4) and breakthrough pain (p = 0.49). The correlation between pain response after radiotherapy and SINS was statistically significant for both pain at rest (p = 0.007) and breakthrough pain (p = 0.047). Discussion/conclusion. The degree of instability, classified according to SINS, resulted to be predictive factor for pain response after radiotherapy. SINS might become a valid tool to identify those patients who can benefit the most from radiotherapy (AU)

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The spine instability neoplastic score (SINS) in the assessment of response to radiotherapy for bone metastases.

BACKGROUND: Vertebral metastases are often causing pain and spine instability. Radiotherapy is of significant benefit for painful spine metastases but the response can be very variable. The spine instability neoplastic score (SINS) is a recent classification system for diagnosis of spinal instability caused by vertebral metastases. We analysed the degree of pain relief, the need of drug therapy and the imaging features and the SINS before and after radiotherapy. In particular, we investigated the possible correlation of spine instability defined by pre-treatment SINS with pretreatment pain and with response to radiotherapy. MATERIAL/METHODS: This study included 121 patients with spine metastases treated with palliative 3D conformal radiotherapy. Pain "at rest" and "breakthrough pain", need for drug therapy in terms of "anti-inflammatory", "weak opioid", "strong opioid", imaging studies and SINS were assessed before and after radiotherapy. Statistical analysis was performed by the correlation coefficient of Spearman and Kruskal-Wallis test. RESULTS: Pain relief after radiotherapy was observed in 50.4 and 57.8% of patients in terms of pain at rest and breakthrough pain, respectively. The correlation between pain before radiotherapy and SINS was not statistically significant for both pain at rest (p = 0.4) and breakthrough pain (p = 0.49). The correlation between pain response after radiotherapy and SINS was statistically significant for both pain at rest (p = 0.007) and breakthrough pain (p = 0.047). DISCUSSION/CONCLUSION: The degree of instability, classified according to SINS, resulted to be predictive factor for pain response after radiotherapy. SINS might become a valid tool to identify those patients who can benefit the most from radiotherapy.

Quality of life in patients treated by adjuvant radiotherapy for endometrial and cervical cancers: correlation with dose-volume parameters

Introduction: Modern multidisciplinary cancer treatments aim at obtaining minimal influence on patients’ quality of life (QoL). The purpose of this study was to assess QoL and correlate it with dose-volume parameters of organ at risks (OARs) in patients who received adjuvant radiotherapy for endometrial and cervical cancers. Materials and methods: We administered the EORTC QLQ-C30 and EN24 or CX24 questionnaires to 124 patients, 100 with endometrial cancer and 24 with cervical cancer treated with postoperative radiotherapy ± chemotherapy in regular follow-up. Bladder function, fecal incontinence or urgency and sexual functioning were investigated and correlated with dose-volume parameters of OAR by multiple linear regression analysis. This correlation was assessed by R2 value. Results: QoL was very high in the majority of patients (82.3 % of patients). Few patients referred urinary incontinence (3.2 %) or abdominal discomfort of high grade (4.0 %). We found a significant correlation between bladder V40, i.e., absolute percentage of bladder volume that received a dose of 40 Gy, and global health status (p < 0.05, R 2 = 0.17), urinary urgency (p < 0.05, R 2 = 0.24), urinary incontinence (p < 0.05, R 2 = 0.23) and dyspareunia (p < 0.05, R 2 = 0.04). We found also a correlation between global health status and mean dose to vagina (p < 0.05, R 2 = 0.17) and between maximum dose to lumbo-sacral plexus and abdominal pain (p < 0.05, R 2 = 0.07). Conclusions: Women treated with surgery and adjuvant radiotherapy for endometrial and cervical cancers have good QoL with minimal limitations of daily activities. QoL was correlated with dose-volume parameters such as bladder V40, mean dose to vagina, maximum dose to trigone and LSP

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Common European Mitochondrial Haplogroups in the Risk for Radiation-induced Subcutaneous Fibrosis in Breast Cancer Patients.

AIMS: The contribution of mitochondrial DNA (mtDNA) variations to clinical radiosensitivity is largely unknown. In the present study, we evaluated the association between mtDNA haplogroups and the risk of radiation-induced subcutaneous fibrosis after postoperative radiotherapy in breast cancer patients. MATERIALS AND METHODS: Subcutaneous fibrosis was scored according to the Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA) scale in 286 Italian breast cancer patients who received radiotherapy after breast-conserving surgery. Eight mtDNA single nucleotide polymorphisms that define the nine major haplogroups in the European population were determined by polymerase chain reaction restriction fragment length polymorphism analysis on genomic DNA extracted from peripheral blood. RESULTS: In a Kaplan-Meier analysis evaluated by the Log-rank test, carriers of haplogroup H were found to be at lower risk of grade ≥2 subcutaneous fibrosis (P = 0.018) compared with all other haplotypes combined. In the multivariate Cox regression analysis adjusted for clinical factors (body mass index, breast diameter, adjuvant treatment, dose per fraction, radiation type and acute skin toxicity), haplogroup H emerged as a protective factor for moderate to severe radiation-induced fibrosis at a nominal significance level (hazard ratio: 0.50, 95% confidence interval 0.27-0.92, P = 0.027), which did not survive correction for multiple testing. CONCLUSIONS: Our results suggest a protective effect of the mitochondrial haplogroup H in the development of radiation-induced fibrosis in breast cancer patients. However, the loss of statistical significance after correction for multiple comparisons and the lack of an independent validation cohort make our findings preliminary, requiring further confirmation in large-scale prospective studies.

Quality of life in patients treated by adjuvant radiotherapy for endometrial and cervical cancers: correlation with dose-volume parameters.

INTRODUCTION: Modern multidisciplinary cancer treatments aim at obtaining minimal influence on patients' quality of life (QoL). The purpose of this study was to assess QoL and correlate it with dose-volume parameters of organ at risks (OARs) in patients who received adjuvant radiotherapy for endometrial and cervical cancers. MATERIALS AND METHODS: We administered the EORTC QLQ-C30 and EN24 or CX24 questionnaires to 124 patients, 100 with endometrial cancer and 24 with cervical cancer treated with postoperative radiotherapy ± chemotherapy in regular follow-up. Bladder function, fecal incontinence or urgency and sexual functioning were investigated and correlated with dose-volume parameters of OAR by multiple linear regression analysis. This correlation was assessed by R (2) value. RESULTS: QoL was very high in the majority of patients (82.3 % of patients). Few patients referred urinary incontinence (3.2 %) or abdominal discomfort of high grade (4.0 %). We found a significant correlation between bladder V40, i.e., absolute percentage of bladder volume that received a dose of 40 Gy, and global health status (p < 0.05, R (2) = 0.17), urinary urgency (p < 0.05, R (2) = 0.24), urinary incontinence (p < 0.05, R (2) = 0.23) and dyspareunia (p < 0.05, R (2) = 0.04). We found also a correlation between global health status and mean dose to vagina (p < 0.05, R (2) = 0.17) and between maximum dose to lumbo-sacral plexus and abdominal pain (p < 0.05, R (2) = 0.07). CONCLUSIONS: Women treated with surgery and adjuvant radiotherapy for endometrial and cervical cancers have good QoL with minimal limitations of daily activities. QoL was correlated with dose-volume parameters such as bladder V40, mean dose to vagina, maximum dose to trigone and LSP.

Interstitial brachytherapy for eyelid carcinoma. Outcome analysis in 60 patients.

BACKGROUND: Eyelid cancer is a therapeutic challenge due to the cosmetic and functional implications of this anatomical region and the objectives of therapy are tumor control, functional and cosmetic outcome. AIM: The present study was performed to analyze local control, toxicity, functional and cosmetic results in patients with eyelid carcinoma treated by interstitial brachytherapy. MATERIAL AND METHODS: In this study 60 patients with eyelid carcinoma were treated by interstitial brachytherapy using iridium ((192)Ir) wires with a linear activity of 1.2-1.7 mCi/cm. The prescription dose was 51-70 Gy (mean 65 Gy, median 66 Gy). RESULTS: Of the 60 patients 51 (85.0 %) had received no prior treatment, 4 (6.7 %) had received previous surgery with positive or close margins and 5 (8.3 %) had suffered local recurrence after surgery. Of the tumors 52 (86.7 %) were basal cell carcinoma, 7 (11.7 %) squamous cell carcinoma and 1 (1.7 %) Merkel cell carcinoma. Clinical stage of the 51 previously untreated tumors was 38 T1N0, 12 T2N0 and 1 T3N0. Mean follow-up was 92 months (range 6-253 months). Local control was maintained in 96.7 % of patients. Late effects higher than grade 2 were observed in 3.0 % of cases. Functional and cosmetic outcomes were optimal in 68.4 % of patients. CONCLUSION: Interstitial brachytherapy for carcinoma of the eyelid can achieve local control, cosmetic and functional results comparable to those of surgery.

Dysphagia after definitive radiotherapy for head and neck cancer. Correlation of dose-volume parameters of the pharyngeal constrictor muscles.

BACKGROUND: Dysphagia is a complication of head and neck cancer patients undergoing radiotherapy (RT). We analysed frequency and severity of swallowing dysfunction and correlated these findings with dose-volume histograms (DVHs) of the pharyngeal constrictor muscles. METHODS: A total of 50 patients treated by radical RT were enrolled. DVHs of constrictor muscles were correlated with acute and late dysphagia and with the items of three quality of life questionnaires. RESULTS: Mean dose to superior and middle constrictor muscles (SCM, MCM), partial volume of SCM and MCM receiving a dose ≥ 50 Gy dose to the whole constrictor muscles ≥ 60 Gy and tumour location were associated to late dysphagia at univariate analysis. Mean dose to the MCM was the only statistically significant predictor of late dysphagia at the multivariable analysis. CONCLUSION: The study shows a significant relationship between long-term dysphagia and mean doses to SCM, MCM, whole constrictor muscles, and oropharyngeal tumour. This finding suggests a potential advantage in reducing the RT dose to swallowing structures to avoid severe dysphagia.

Hydrophobic organization of membrane proteins.

Membrane-exposed residues are more hydrophobic than buried interior residues in the transmembrane regions of the photosynthetic reaction center from Rhodobacter sphaeroides. This hydrophobic organization is opposite to that of water-soluble proteins. The relative polarities of interior and surface residues of membrane and water soluble proteins are not simply reversed, however. The hydrophobicities of interior residues of both membrane and water-soluble proteins are comparable, whereas the bilayer-exposed residues of membrane proteins are more hydrophobic than the interior residues, and the aqueous-exposed residues of water-soluble proteins are more hydrophilic than the interior residues. A method of sequence analysis is described, based on the periodicity of residue replacement in homologous sequences, that extends conclusions derived from the known atomic structure of the reaction center to the more extensive database of putative transmembrane helical sequences.