CT radiomic predictors of local relapse after SBRT for lung oligometastases from colorectal cancer: a single institute pilot study.

OBJECTIVES: To assess the potential of radiomic features (RFs) extracted from simulation computed tomography (CT) images in discriminating local progression (LP) after stereotactic body radiotherapy (SBRT) in the management of lung oligometastases (LOM) from colorectal cancer (CRC). MATERIALS AND METHODS: Thirty-eight patients with 70 LOM treated with SBRT were analyzed. The largest LOM was considered as most representative for each patient and was manually delineated by two blinded radiation oncologists. In all, 141 RFs were extracted from both contours according to IBSI (International Biomarker Standardization Initiative) recommendations. Based on the agreement between the two observers, 134/141 RFs were found to be robust against delineation (intraclass correlation coefficient [ICC] > 0.80); independent RFs were then assessed by Spearman correlation coefficients. The association between RFs and LP was assessed with Mann-Whitney test and univariate logistic regression (ULR): the discriminative power of the most informative RF was quantified by receiver-operating characteristics (ROC) analysis through area under curve (AUC). RESULTS: In all, 15/38 patients presented LP. Median time to progression was 14.6 months (range 2.4-66 months); 5/141 RFs were significantly associated to LP at ULR analysis (p < 0.05); among them, 4 RFs were selected as robust and independent: Statistical_Variance (AUC = 0.75, p = 0.002), Statistical_Range (AUC = 0.72, p = 0.013), Grey Level Size Zone Matrix (GLSZM) _zoneSizeNonUniformity (AUC = 0.70, p = 0.022), Grey Level Dependence Zone Matrix (GLDZM) _zoneDistanceEntropy (AUC = 0.70, p = 0.026). Importantly, the RF with the best performance (Statisical_Variance) is simply representative of density heterogeneity within LOM. CONCLUSION: Four RFs extracted from planning CT were significantly associated with LP of LOM from CRC treated with SBRT. Results encourage further research on a larger population aiming to define a usable radiomic score combining the most predictive RFs and, possibly, additional clinical features.

External validation of an 18F-FDG-PET radiomic model predicting survival after radiotherapy for oropharyngeal cancer.

PURPOSE/OBJECTIVE: The purpose of the study is to externally validate published 18F-FDG-PET radiomic models for outcome prediction in patients with oropharyngeal cancer treated with chemoradiotherapy. MATERIAL/METHODS: Outcome data and pre-radiotherapy PET images of 100 oropharyngeal cancer patients (stage IV:78) treated with concomitant chemotherapy to 66-69 Gy/30 fr were available. Tumors were segmented using a previously validated semi-automatic method; 450 radiomic features (RF) were extracted according to IBSI (Image Biomarker Standardization Initiative) guidelines. Only one model for cancer-specific survival (CSS) prediction was suitable to be independently tested, according to our criteria. This model, in addition to HPV status, SUVmean and SUVmax, included two independent meta-factors (Fi), resulting from combining selected RF clusters. In a subgroup of 66 patients with complete HPV information, the global risk score R was computed considering the original coefficients and was tested by Cox regression as predictive of CSS. Independently, only the radiomic risk score RF derived from Fi was tested on the same subgroup to learn about the radiomics contribution to the model. The metabolic tumor volume (MTV) was also tested as a single predictor and its prediction performances were compared to the global and radiomic models. Finally, the validation of MTV and the radiomic score RF were also tested on the entire dataset. RESULTS: Regarding the analysis of the subgroup with HPV information, with a median follow-up of 41.6 months, seven patients died due to cancer. R was confirmed to be associated to CSS (p value = 0.05) with a C-index equal 0.75 (95% CI=0.62-0.85). The best cut-off value (equal to 0.15) showed high ability in patient stratification (p=0.01, HR=7.4, 95% CI=1.6-11.4). The 5-year CSS for R were 97% (95% CI: 93-100%) vs 74% (56-92%) for low- and high-risk groups, respectively. RF and MTV alone were also significantly associated to CSS for the subgroup with an almost identical C-index. According to best cut-off value (RF>0.12 and MTV>15.5cc), the 5-year CSS were 96% (95% CI: 89-100%) vs 65% (36-94%) and 97% (95% CI: 88-100%) vs 77% (58-93%) for RF and MTV, respectively. Results regarding RF and MTV were confirmed in the overall group. CONCLUSION: A previously published PET radiomic model for CSS prediction was independently validated. Performances of the model were similar to the ones of using only the MTV, without improvement of prediction accuracy.

Management of radiation-induced oral mucositis in head and neck cancer patients: a real-life survey among 25 Italian radiation oncology centers.

AIM: Radiation-induced oral mucositis (RIOM) is the most frequent side effect in head and neck cancer (HNC) patients treated with curative radiotherapy (RT). A standardized strategy for preventing and treating RIOM has not been defined. Aim of this study was to perform a real-life survey on RIOM management among Italian RT centers. METHODS: A 40-question survey was administered to 25 radiation oncologists working in 25 different RT centers across Italy. RESULTS: A total of 1554 HNC patients have been treated in the participating centers in 2021, the majority (median across the centers 91%) with curative intent. Median treatment time was 41 days, with a mean percentage of interruption due to toxicity of 14.5%. Eighty percent of responders provide written oral cavity hygiene recommendations. Regarding RIOM prevention, sodium bicarbonate mouthwashes, oral mucosa barrier agents, and hyaluronic acid-based mouthwashes were the most frequent topic agents used. Regarding RIOM treatment, 14 (56%) centers relied on literature evidence, while internal guidelines were available in 13 centers (44%). Grade (G)1 mucositis is mostly treated with sodium bicarbonate mouthwashes, oral mucosa barrier agents, and steroids, while hyaluronic acid-based agents, local anesthetics, and benzydamine were the most used in mucositis G2/G3. Steroids, painkillers, and anti-inflammatory drugs were the most frequent systemic agents used independently from the RIOM severity. CONCLUSION: Great variety of strategies exist among Italian centers in RIOM management for HNC patients. Whether different strategies could impact patients' compliance and overall treatment time of the radiation course is still unclear and needs further investigation.

Monitoring skin dose changes during image-guided helical tomotherapy for head and neck cancer patients.

PURPOSE: An increase of skin dose during head and neck cancer (HNC) radiotherapy is potentially dangerous. Aim of this study was to quantify skin dose variation and to assess the need of planning adaptation (ART) to counteract it. METHODS: Planning CTs of 32 patients treated with helical tomotherapy (HT) according to a Simultaneous Integrated Boost (SIB) technique delivering 54/66 Gy in 30 fractions were deformably co-registered to MVCTs taken at fractions 15 and 30; in addition, the first fraction was also considered. The delivered dose-of-the-day was calculated on the corresponding deformed images. Superficial body layers (SL) were considered as a surrogate for skin, considering a layer thickness of 2 mm. Variations of SL DVH (∆SL) during therapy were quantified, focusing on ∆SL95% (i.e., 62.7 Gy). RESULTS: Small changes (within ± 1 cc for ∆SL95%) were seen in 15/32 patients. Only 2 patients experienced ∆SL95% > 1 cc in at least one of the two monitored fractions. Negative ∆SL95% > 1 cc (up to 17 cc) were much more common (15/32 patients). The trend of skin dose changes was mostly detected at the first fraction. Negative changes were correlated with the presence of any overlap between PTV and SL at planning and were explained in terms of how the planning system optimizes the PTV dose coverage near the skin. Acute toxicity was associated with planning DVH and this association was not improved if considering DVHs referring to fractions 15/30. CONCLUSION: About half of the patients treated with SIB with HT for HNC experienced a skin-sparing effect during therapy; only 6% experienced an increase. Our findings do not support skin-sparing ART, while suggesting the introduction of improved skin-sparing planning techniques.

Toxicity and efficacy of salvage carbon 11-choline positron emission tomography/computed tomography-guided radiation therapy in patients with lymph node recurrence of prostate cancer.

OBJECTIVE: To report the 3-year toxicity and outcomes of carbon 11 (11C)-choline-positron emission tomography (PET)/computed tomography (CT)-guided radiotherapy (RT), delivered via helical tomotherapy (HTT; Tomotherapy® Hi-Art II® Treatment System, Accuray Inc., Sunnyvale, CA, USA) after lymph node (LN) relapses in patients with prostate cancer. PATIENTS AND METHODS: From January 2005 to March 2013, 81 patients with biochemical recurrence after surgery, with or without adjuvant/salvage RT or radical RT, and with evidence of LN 11C-choline-PET/CT pathological uptake, underwent HTT (median [range] prostate-specific antigen level 2.59 [0.61-187] ng/mL). Of the 81 patients, 72 were treated at the pelvic and/or lumbar-aortic LN chain with HTT at 51.8 Gy/28 fr and with simultaneous integrated boost to a median dose of 65.5 Gy on the pathological uptake sites detected by 11C-choline-PET/CT. Nine patients were treated without simultaneous integrated boost (50-65.5 Gy, 25-30 fr). RESULTS: With a median (range) follow-up of 36 (9-116) months, 91.4% of the patients had a PSA reduction 3 months after HTT. The 3-year overall, local relapse-free and clinical relapse-free survival rates were 80.0, 89.8 and 61.8%, respectively. The 3-year actuarial incidences of ≥grade 2 rectal and ≥grade 2 genitourinary toxicity were 6.6% (±2.9%) and 26.3% (±5.5%), respectively. A PSA nadir of ≥0.26 ng/mL (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.7-7.7; P = 0.001), extrapelvic 11C-choline-PET/CT-positive LN location (HR 2.4, 95% CI 0.9-6.4; P = 0.07), RT previous to HTT (HR 2.7; 95% CI 1.07-6.9, P = 0.04) and number of positive LNs (HR 1.13, 95% CI 1.04-1.22; P = 0.003) were the main predictors of clinical relapse after HTT. CONCLUSIONS: 11C-choline-PET/CT-guided HTT is safe and effective in the treatment of LN relapses of prostate cancer in previously treated patients.

Early volume variation of positive lymph nodes assessed by in-room mega voltage CT images predicts risk of loco-regional relapses in head and neck cancer patients treated with intensity-modulated radiotherapy.

BACKGROUND: We investigated the possibility to early identify non-responding patients based on FDG-PET positive lymph nodes (PNs) volume variation assessed with in-room images. MATERIAL AND METHODS: Twenty-seven head and neck cancer patients with at least one pre-treatment PNs were retrospectively analyzed; they received 54 Gy, 66 Gy, 69 Gy in 30 fractions on precautionary lymph nodal (N), primary (T) and PET positive (BTV) planning target volumes (PTVs), respectively with Helical TomoTherapy (SIB approach). PNs volume changes during treatment were assessed based on megavoltage computed tomography (MVCT) used for image guidance as ratio between volumes at fractions 10/20/30 and at first fraction. Data on T, N and M relapses (rT, rN, rM) were collected for all patients. The difference of PNs volume changes, during treatment, between patients with versus without relapses was tested (Mann-Whitney test). The impact of shrinkage on the corresponding survival curves (Cox proportional-hazard regression), dividing between no/moderate versus large shrinkage (based on ROC curve best cut-off value) was also investigated. RESULTS: Median follow-up was 27.4 m (3.7-108.9). The numbers for rT, rN, rM were 5, 4, 6, respectively. Differences in PNs shrinkage were found between patients with and without rT/rN at all considered timing [fr 20, rT: 0.56 vs. 1.07 (median), p = 0.06; rN: 0.57 vs. 1.25, p = 0.07]. Differences were lower for rM. Survival curves provide high hazard ratios (HR) between PNs changes and rT/rN at all considered timing [fr 20, rT: best cut-off = 0.58, HR 5.1 (95% CI 0.5-49.4), p = 0.12; rN: best cut-off = 0.98, HR 14.9 (1.6-142.9), p = 0.01]. CONCLUSION: A limited shrinkage of PNs during treatment is associated with poorer outcome in terms of T/N relapses. The early variation of PNs observed on in-room images may provide useful information about the individual response with potential application in guiding an early adaptation of the treatment.

Impact of low skeletal muscle mass in oropharyngeal cancer patients treated with radical chemo-radiotherapy: A mono-institutional experience.

AIMS: Low skeletal muscle mass index (SMI) has recently emerged as an independent prognostic factor in oncological patients and it is linked with poor survival and higher treatment toxicity. The present study aims to determine the possible impact of low SMI on survival and acute toxicity in oropharyngeal patients. METHODS: Seventy-six patients with locally advanced oropharyngeal squamous cell carcinoma (stage III-IVC) were treated in our institution with Helical TomoTherapy® (HT - Accuray, Maddison, WI, USA) between 2005 and 2021. All patients received concomitant platinum-based chemotherapy (CT) (at least 200 mg/m2). The SMI was determined using the calculation of cross-sectional area at C3. Twenty patients (26%) presented pre-treatment low SMI, according to Chargi definitions. RESULTS: All patients concluded the treatment. Thirteen patients with low SMI (65%) and 22 patients with normal SMI (39%) presented acute toxicity greater than or equal to grade 3, but this difference was not statistically significant (p-value = 0.25). Overall survival was analyzed in 65 patients, excluding those who finished CT-RT less than six months before the analysis. Overall survival was significantly lower in low SMI versus normal SMI patients (p-value = 0.035). Same difference was observed in N0-N2a patients, suggesting an important role of SMI also in lower nodal burden and putatively better prognosis. CONCLUSIONS: Although the results are limited to a small population, our case series has the advantage to be very homogeneous in patients and treatment characteristics. In our setting, SMI demonstrated a crucial impact on overall survival. Further investigation with larger samples is necessary to confirm our results to improve patient outcomes.

Acute kidney injury and acute kidney disease in high-dose cisplatin-treated head and neck cancer.

Background: In locally advanced head and neck squamous cell carcinoma (LA-SCCHN) at least 200mg/m2 (standard dose 300 mg/m2) of cisplatin concomitant with radiotherapy represents the standard of care, both in postoperative and conservative settings. Nevertheless, high dose administration every 3 weeks is often replaced with low dose weekly cisplatin to avoid toxicities like kidney injury, though often failing to reach the therapeutic dose. Our aim was to investigate the incidence of renal impairment in the real-life setting, integrating high dose cisplatin with adequate supportive therapy, and to explore both Acute Kidney Injury (AKI) and Acute Kidney Disease (AKD), a recently described clinical renal syndrome that encompasses functional alterations of the kidney lasting fewer than 3 months. Methods: One hundred and nine consecutive patients affected by LA-SCCHN and treated with at least a cumulative dosage of 200 mg/m2 of cisplatin concomitant with radiotherapy were enrolled in this prospective observational study. Results: AKI was reported in 12.8% of patients, 50% of whom were stage 1 (KDIGO criteria), while 25.7% of the cohort developed AKD. Patients with baseline estimated Glomerular Filtration Rate (eGFR) < 90 ml/min showed a higher incidence of AKD (36.2% vs 17.7%). Hypertension, baseline eGFR, and therapy with Renin-angiotensin-aldosterone system inhibitors proved to be significant factors associated with both AKI and AKD. Conclusion: AKI and AKD are not rare complications of high-dose cisplatin, but an appropriate prevention strategy and accurate monitoring of patients during treatment could lead to a reduction of the burden of these conditions.

Patients with Cardiac Implantable Electronic Device Undergoing Radiation Therapy: Insights from a Ten-Year Tertiary Center Experience.

BACKGROUND: The number of patients with cardiac implantable electronic devices (CIEDs) receiving radiotherapy (RT) is increasing. The management of CIED-carriers undergoing RT is challenging and requires a collaborative multidisciplinary approach. AIM: The aim of the study is to report the real-world, ten-year experience of a tertiary multidisciplinary teaching hospital. METHODS: We conducted an observational, real-world, retrospective, single-center study, enrolling all CIED-carriers who underwent RT at the San Raffaele University Hospital, between June 2010 and December 2021. All devices were MRI-conditional. The devices were programmed to an asynchronous pacing mode for patients who had an intrinsic heart rate of less than 40 beats per minute. An inhibited pacing mode was used for all other patients. All tachyarrhythmia device functions were temporarily disabled. After each RT session, the CIED were reprogrammed to the original settings. Outcomes included adverse events and changes in the variables that indicate lead and device functions. RESULTS: Between June 2010 and December 2021, 107 patients were enrolled, among which 63 (58.9%) were pacemaker carriers and 44 (41.1%) were ICD carriers. Patients were subjected to a mean of 16.4 (±10.7) RT sessions. The most represented tumors in our cohort were prostate cancer (12; 11%), breast cancer (10; 9%) and lung cancer (28; 26%). No statistically significant changes in device parameters were recorded before and after radiotherapy. Generator failures, power-on resets, changes in pacing threshold or sensing requiring system revision or programming changes, battery depletions, pacing inhibitions and inappropriate therapies did not occur in our cohort of patients during a ten-year time span period. Atrial arrhythmias were recorded during RT session in 14 patients (13.1%) and ventricular arrhythmias were observed at device interrogation in 10 patients (9.9%). CONCLUSIONS: Changes in device parameters and arrhythmia occurrence were infrequent, and none resulted in a clinically significant adverse event.

Toxicity of Hypofractionated Whole Breast Radiotherapy Without Boost and Timescale of Late Skin Responses in a Large Cohort of Early-Stage Breast Cancer Patients.

AIM: To report toxicity of hypofractionated whole-breast radiotherapy in a large cohort of early-stage breast cancer (BCaients. MATERIALS AND METHODS: From 02/2009-05/2017, 1325 consecutive BCa patients were treated with 40.05 Gy/15 fractions, without boost. Median age was 62 (IQR:51.1-70.5) years. Chemotherapy was prescribed for 28% of patients, hormonal therapy for 80.3%, monoclonal antibodies for 8.2%. RESULTS: Median follow-up was 72.4 (IQR: 44.6-104.1) months. Acute RTOG toxicity was: 69.8% Grade (G) 1, 14.3% G2 and 1.7% G3. Late SOMA-LENT toxicities were: edema-hyperpigmentation (E-H): G1 28.67%, G2 4.41%, G3 0.15%; fibrosis-atrophy-telangiectasia-pain (F-A-T-P): G1 14.6%, G2 3.2%, G3 0.8%, G4 0.1%. Median time to first occurrence was 6 and 18 months, respectively. Aesthetic result after surgery was excellent in 28.7%, good in 41.5%, acceptable in 20.3% and poor in 9.5% of patients. Change in breast appearance after radiotherapy was mild in 6.9%, moderate in 2.3% and marked in 1.3% of patients. Concomitant chemotherapy, obesity, smoking, use of bolus and planning target volume (PTV) were associated with higher acute toxicity. Patients ≥55 years old were less likely to experience acute toxicity. PTV and acute G2 toxicity were associated with ≥G2 E-H. PTV, concomitant chemotherapy, hypertension and ≥G2 acute toxicity were associated with increased risk of F-A-T-P. CONCLUSION: Hypofractionated whole-breast radiotherapy without boost demonstrated mild acute and late toxicity in a large cohort of consecutive patients. Moderate and marked changes in breast appearance were registered for 3.6% of patients and occurred between 18 to 42 months.

PET-guided dose escalation tomotherapy in malignant pleural mesothelioma.

PURPOSE: To test the feasibility of salvage radiotherapy using PET-guided helical tomotherapy in patients with progressive malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: A group of 12 consecutive MPM patients was treated with 56 Gy/25 fractions to the planning target volume (PTV); FDG-PET/CT simulation was always performed to include all positive lymph nodes and MPM infiltrations. Subsequently, a second group of 12 consecutive patients was treated with the same dose to the whole pleura adding a simultaneous integrated boost of 62.5 Gy to the FDG-PET/CT positive areas (BTV). RESULTS: Good dosimetric results were obtained in both groups. No grade 3 (RTOG/EORTC) acute or late toxicities were reported in the first group, while 3 cases of grade 3 late pneumonitis were registered in the second group: the duration of symptoms was 2-10 weeks. Median overall survival was 8 months (1.2-50.5 months) and 20 months (4.3-33.8 months) from the beginning of radiotherapy, for groups I and II, respectively (p=0.19). A significant impact on local relapse from radiotherapy was seen (median time to local relapse: 8 vs 17 months; 1-year local relapse-free rate: 16% vs 81%, p=0.003). CONCLUSIONS: The results of this pilot study support the planning of a phase III study of combined sequential chemoradiotherapy with dose escalation to BTV in patients not able to undergo resection.

Ten Year Results of Extensive Nodal Radiotherapy and Moderately Hypofractionated Simultaneous Integrated Boost in Unfavorable Intermediate-, High-, and Very High-Risk Prostate Cancer.

AIMS: To report 10-year outcomes of WPRT and HD moderately hypofractionated SIB to the prostate in UIR, HR, and VHR PCa. METHODS: From 11/2005 to 12/2015, 224 UIR, HR, and VHR PCa patients underwent WPRT at 51.8 Gy/28 fractions and SIB at 74.2 Gy (EQD2 88 Gy) to the prostate. Androgen deprivation therapy (ADT) was prescribed in up to 86.2% of patients. RESULTS: Median follow-up was 96.3 months (IQR: 71-124.7). Median age was 75 years (IQR: 71.3-78.1). At last follow up, G3 GI-GU toxicity was 3.1% and 8%, respectively. Ten-year biochemical relapse-free survival (bRFS) was 79.8% (95% CI: 72.3-88.1%), disease-free survival (DFS) 87.8% (95% CI: 81.7-94.3%), overall survival (OS) 65.7% (95% CI: 58.2-74.1%), and prostate cancer-specific survival (PCSS) 94.9% (95% CI: 91.0-99.0%). Only two patients presented local relapse. At univariate analysis, VHR vs. UIR was found to be a significant risk factor for biochemical relapse (HR: 2.8, 95% CI: 1.17-6.67, p = 0.021). After model selection, only Gleason Score ≥ 8 emerged as a significant factor for biochemical relapse (HR = 2.3, 95% CI: 1.12-4.9, p = 0.023). Previous TURP (HR = 3.5, 95% CI: 1.62-7.54, p = 0.001) and acute toxicity ≥ G2 (HR = 3.1, 95% CI = 1.45-6.52, p = 0.003) were significant risk factors for GU toxicity ≥ G3. Hypertension was a significant factor for GI toxicity ≥ G3 (HR = 3.63, 95% CI: 1.06-12.46, p = 0.041). ADT (HR = 0.31, 95% CI: 0.12-0.8, p = 0.015) and iPsa (HR = 0.37, 95% CI: 0.16-0.83, p = 0.0164) played a protective role. CONCLUSIONS: WPRT and HD SIB to the prostate combined with long-term ADT, in HR PCa, determine good outcomes with acceptable toxicity.

Impact of molecular subtype on 1325 early-stage breast cancer patients homogeneously treated with hypofractionated radiotherapy without boost: Should the indications for radiotherapy be more personalized?

AIM: We report molecular subtype impact on 1325 early breast cancer (BCa) patients treated with whole breast hypofractionated (WBH) adjuvant forward-planned intensity modulated radiotherapy (F-IMRT) without boost. METHODS AND MATERIALS: From 02/2009-05/2017 1325 patients with pTis-pT3, pNx-N1aM0 BCa who underwent breast conservation surgery were treated with WBHF-IMRT in our institute, to a total dose of 40 Gy/15 fractions, without boost. Median age: 62 (interquartile range-IQR-:51.14-70.53) years. HISTOLOGY: 8% in situ carcinoma (ISC), 92% invasive tumors. Molecular subtypes (invasive tumors): 49.9% Luminal A, 33.1% Luminal B Her2 negative (-), 6.2% Luminal B Her2 positive (+), 3.6% Hormone Receptor (HR)- Her2+, 7.1% Triple negative (TNBC), and 0.2% HR+. Chemotherapy (CT) was prescribed in 28% of patients, hormonal therapy in 80.3%, monoclonal antibodies (MAb) in 86.8% of Luminal B Her2+ and 97.7% of HR- Her2+ patients. RESULTS: Median follow up was 72.43 (IQR: 44.63-104.13) months. The 5-year Kaplan-Meier estimates of local relapse-free survival (LRFS) was 97.8%, regional-(RRFS) 98.6%, loco-regional- (LRRFS) 96.9%, distant- (DRFS) 96.6%, disease-free survival (DFS) 94.8% and overall survival (OS) 95.5%. Considering molecular subtypes, 5-year LRFS was: 99.8% for Luminal A, 96.7% for Luminal B Her2-, 94.1% for Luminal B Her2+, 87.9% for HR- Her2+, 95.1% for TNBC and 99.1% for in situ carcinoma. CONCLUSION: While the overall estimated probability of LR within 5 years after WBHF-IMRT without boost is good (2.2%), molecular subtypes have a strong impact, despite MAb therapy in Her2+ patients, and CT for TNBC patients, and could be used as a parameter in deciding the boost prescription.

Uncommon Site of Metastasis and Prolonged Survival in Patients with Anaplastic Thyroid Carcinoma: A Systematic Review of the Literature.

Anaplastic thyroid carcinoma (ATC) is a very rare, highly aggressive malignant thyroid tumor with an overall survival from 3 to 5 months in most of the cases. Even the modern and intensive treatments seem not to be enough to provide a cure, also for the resectable ones, and the role of chemotherapy is still unclear but does not seem to prolong survival. Nevertheless, some patients survive longer and have a better outcome, even in the presence of metastasis, than what the literature reports. We present the case of a 64-year-old female affected by ATC, treated on February 2018 with surgery followed by chemoradiation. One year after surgery, the patient developed a subcutaneous recurrence that was radically resected and is still alive 29 months after the diagnosis. We propose a systematic review of the literature to deepen the knowledge of the prognostic factors of ATC with the aim to recognize and select the patients with a better outcome, even if metastatic, and to describe a very uncommon site of metastatization.

Radiosurgery and fractionated stereotactic radiotherapy in oligometastatic/oligoprogressive non-small cell lung cancer patients: Results of a multi-institutional series of 198 patients treated with "curative" intent.

OBJECTIVES: stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) are a therapeutic option for Oligometastatic/Oligoprogressive (OM/OP) NSCLC. This retrospective multicentre analysis aims to analyse clinical outcomes and treatment related toxicity of patients treated to all sites of know disease with SRS and/or FSRT for OM/OP NSCLC in 8 Italian radiation oncology centres. MATERIALS AND METHODS: From January 2016 to January 2017 198 OM/OP NSCLC patients (pts) were treated in 8 Centres. Inclusion criteria were as follows: 1-5 lesions at onset or after previous systemic treatment; Pts must have all metastatic lesions treated. Endpoints analysed were local progression free survival (LPFS); out-of-field recurrence free survival (OFPS); progression free survival (PFS); overall survival (OS). Time to New systemic Therapy free survival (TNT) and toxicity were also analysed. RESULTS: At the time of radiotherapy, 119 pts (60 %) were treated for a single lesion, 49 (25 %) for 2 lesions, 30 (15 %) for 3-5 metastases. Total number of lesions treated was 333: 204 brain, 68 lung, 24 bone, 16 nodal, 12 adrenal, 8 liver and 1 soft tissue. 83/198 pts (41.8 %) had the primary tumour controlled at the time of the SRT. After a median follow-up of 18 months, median OS and PFS were 29.6 months and 10.6 months, respectively. One year LPFS and OPFS were 90 % and 47 %, respectively. Median TNT was 10 months. At univariate analysis factors associated with better OS were PS 0-1; controlled primary tumour, 1-2 lesions; extracranial metastasis. Multivariate analysis confirmed number of lesions <3 and extracranial metastasis to be related with better survival (Relative Risk 0.4 and 0.41, respectively). Two cases of death possibly related to brain radionecrosis were observed. CONCLUSION: OM/OP NSCLC pts treated with an ablative SRT to all metastatic sites have fair outcomes with acceptable toxicity. Better results might be achieved in case of low disease burden and extracranial possibly when primary tumour is controlled.

Moderately Hypofractionated Helical IMRT, FDG-PET/CT-guided, for Progressive Malignant Pleural Mesothelioma in Patients With Intact Lungs.

INTRODUCTION: The objective of this study was to present the outcomes of moderately hypofractionated helical intensity-modulated radiation therapy (HT) with/without simultaneous integrated boost (SIB) on fluorodeoxyglucose-positron emission tomography (FDG-PET) positive areas (gross tumor volume [GTV]-PET) for patients with progressive malignant pleural mesothelioma (MPM) after previous treatments. METHODS AND MATERIALS: From May 2006 to April 2014, 51 patients with a median age of 68.8 years (range, 38.6-82 years) were treated. There were 41 men and 10 women; 43 epithelioid MPM and 8 sarcomatoid, involving the left pleura in 25 patients and the right pleura in 26 patients. The initial stage was: I, 11 patients; II, 14 patients; III, 17 patients; and IV, 9 patients. Chemotherapy was prescribed for 46 patients, for 6 cycles (range, 0-18 cycles). Eighteen patients had pleurectomy/decortication, and 33 had talc pleurodesis. FDG-PET was used for target identification. A median dose of 56 Gy/25 fractions was prescribed to the involved pleura, and SIB to 62.5 Gy to GTV-PET was added in 38 patients. RESULTS: The median survival from diagnosis was 25.8 months (range, 8.4-99.0 months). One patient, treated with SIB, was alive at the October 2017 follow-up. Two cases of grade 5 radiation pneumonitis were registered. A GTV-PET ≤ 205 cc was predictive of late ≥ grade 2 lung toxicity, but also of better survival in stage III and IV disease: 5.9 versus 11.7 months (P = .04). A GTV-PET ≥ 473 cc was predictive of early death (P = .001). CONCLUSIONS: Moderately hypofractionated, FDG-PET guided salvage HT in patients with progressive MPM after previous treatments showed acceptable toxicity and outcome results similar to adjuvant radiotherapy after pleurectomy/decortication, suggesting that the delay of radiotherapy is not detrimental to survival, and has the associated benefit of postponing inherent toxicity.

Intensity-modulated proton therapy versus helical tomotherapy in nasopharynx cancer: planning comparison and NTCP evaluation.

PURPOSE: To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for nasopharynx cancer using a simultaneous integrated boost approach. METHODS AND MATERIALS: The data from 6 patients who had previously been treated with HT were used. A three-beam IMPT technique was optimized in the Hyperion treatment planning system, simulating a "beam scanning" technique. HT was planned using the tomotherapy treatment planning system. Both techniques were optimized to simultaneously deliver 66 Gy in 30 fractions to planning target volume (PTV1; GTV and enlarged nodes) and 54 Gy to PTV2 subclinical, electively treated nodes. Normal tissue complication probability calculation was performed for the parotids and larynx. RESULTS: Very similar PTVs coverage and homogeneity of the target dose distribution for IMPT and HT were found. The conformity index was significantly lower for protons than for photons (1.19 vs. 1.42, respectively). The mean dose to the ipsilateral and contralateral parotid glands decreased by 6.4 Gy and 5.6 Gy, respectively, with IMPT. The volume of mucosa and esophagus receiving > or =20 Gy and > or =30 Gy with IMPT was significantly lower than with HT. The average volume of larynx receiving > or =50 Gy was significantly lower with HT, while for thyroid, it was comparable. The volume receiving > or =30, > or =20, and > or =10 Gy in total body volume decreased with IMPT by 14.5%, 19.4%, and 23.1%, respectively. The normal tissue complication probability for the parotid glands was significantly lower with IMPT for all sets of parameters; however, we also estimated an almost full recovery of the contralateral parotid with HT. The normal tissue complication probability for the larynx was not significantly different between the two irradiation techniques. CONCLUSION: Excellent target coverage, homogeneity within the PTVs, and sparing of the organs at risk were reached with both modalities. IMPT allows for better sparing of most organs at risk at medium-to-low doses.

Treatment planning comparison between conformal radiotherapy and helical tomotherapy in the case of locally advanced-stage NSCLC.

BACKGROUND AND PURPOSE: To investigate the impact of Helical Tomotherapy (HT) upon the dose distribution when compared to our routinely delivered 3D conformal radiotherapy (CRT) in the case of patients affected by stage III non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS: Thirteen stage III inoperable NSCLC patients were scheduled to receive 61.2-70.2Gy, 1.8Gy/fraction. Two treatment techniques (HT and CRT) were considered, and in the case of CRT the dose calculation was performed using both the pencil beam (PB) and Anisotropic Analytical Algorithm (AAA) available on the Varian Eclipse planning system. Dose volume constraints for PTV coverage and OAR sparing were assessed for the HT inverse planning with the highest priority upon PTV coverage and spinal cord sparing. The three plans were compared in terms of dose-volume histograms (DVHs) and normal tissue complication probability (NTCP). A statistical analysis was performed using non-parametric Wilcoxon matched pairs tests. RESULTS: In CRT the use of a less accurate algorithm (PB) decreased the monitor unit number by 2.4%. HT significantly improved dose homogeneity within PTV compared with CRT_AAA. For lung parenchyma V20-V40 were lower with HT, corresponding to a decrease of 7% in the risk of radiation pneumonitis. The volume of the heart and esophagus irradiated to >45-60Gy were reduced using HT plans. For eight PTs with an esophagus-PTV overlap >5%, HT significantly reduced both late and acute esophageal complication probability. CONCLUSIONS: Our findings obtained in stage III NSCLC patients underline that HT guarantees an important sparing of lungs and esophagus, thus HT has the potential to improve therapeutic ratio, when compared with CRT, by means of dose escalation and/or combined treatment strategy. In CRT of locally advanced lung cancers, the use of a more advanced algorithm would give significantly better modeling of target dose and coverage.

Skin dose calculation during radiotherapy of head and neck cancer using deformable image registration of planning and mega-voltage computed tomography scans.

BACKGROUND AND PURPOSE: Head-Neck (HN) patients may experience severe acute skin complications that can cause treatment interruption and increase the risk of late fibrosis. This study assessed a method for accurately monitoring skin dose changes during helical tomotherapy for HN cancer based on deformable image registration of planning computed tomography (CT) and mega-voltage CT (MVCT). MATERIALS AND METHODS: Planning CTs of nine patients were deformably registered to mid-treatment MVCT (MV15) images resulting in CTdef images. The original plans were recalculated on both CTdef and mid-treatment kilo-voltage CT (CT15) taken as ground truth. Superficial layers (SL) of the body with thicknesses of 2, 3 and 5 mm (SL2, SL3, SL5) were considered as derma surrogates. SL V95%, V97%, V98%, V100%, V102%, V105% and V107% of the prescribed PTV dose were extracted for CT15/CTdef and compared (considering patients with skin dose > 95%). For comparison, doses were calculated directly on the calibrated MVCT and analyzed in the same way. RESULTS: Differences between SL2/SL3/SL5 V95%-V107% in CT15/CTdef were very small: for eight of nine patients the difference between the considered SL2 Vd% computed on CTdef and CT15 was less than 1.4 cm3 for all d%. A larger value was found when using MVCT for skin dose calculation (4.8 cm3 for SL2), although CTdef body contour matched CT15 body with accuracy similar to that of MV15. CONCLUSIONS: Deforming the planning CT-to-MVCT was shown to be accurate considering external body contours and skin DVHs. The method was able to accurately identify superficial overdosing.

Quantifying the robustness of [18F]FDG-PET/CT radiomic features with respect to tumor delineation in head and neck and pancreatic cancer patients.

PURPOSE: To investigate the robustness of PET radiomic features (RF) against tumour delineation uncertainty in two clinically relevant situations. METHODS: Twenty-five head-and-neck (HN) and 25 pancreatic cancer patients previously treated with 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT)-based planning optimization were considered. Seven FDG-based contours were delineated for tumour (T) and positive lymph nodes (N, for HN patients only) following manual (2 observers), semi-automatic (based on SUV maximum gradient: PET_Edge) and automatic (40%, 50%, 60%, 70% SUV_max thresholds) methods. Seventy-three RF (14 of first order and 59 of higher order) were extracted using the CGITA software (v.1.4). The impact of delineation on volume agreement and RF was assessed by DICE and Intra-class Correlation Coefficients (ICC). RESULTS: A large disagreement between manual and SUV_max method was found for thresholds  ≥50%. Inter-observer variability showed median DICE values between 0.81 (HN-T) and 0.73 (pancreas). Volumes defined by PET_Edge were better consistent with the manual ones compared to SUV40%. Regarding RF, 19%/19%/47% of the features showed ICC < 0.80 between observers for HN-N/HN-T/pancreas, mostly in the Voxel-alignment matrix and in the intensity-size zone matrix families. RFs with ICC < 0.80 against manual delineation (taking the worst value) increased to 44%/36%/61% for PET_Edge and to 69%/53%/75% for SUV40%. CONCLUSIONS: About 80%/50% of 72 RF were consistent between observers for HN/pancreas patients. PET_edge was sufficiently robust against manual delineation while SUV40% showed a worse performance. This result suggests the possibility to replace manual with semi-automatic delineation of HN and pancreas tumours in studies including PET radiomic analyses.