Early regression index (ERI) on MR images as response predictor in esophageal cancer treated with neoadjuvant chemo-radiotherapy: Interim analysis of the prospective ESCAPE trial.

PURPOSE: The early regression index (ERI) predicts treatment response in rectal cancer patients. Aim of current study was to prospectively assess tumor response to neoadjuvant chemo-radiotherapy (nCRT) of locally advanced esophageal cancer using ERI, based on MRI. MATERIAL AND METHODS: From January 2020 to May 2023, 30 patients with esophageal cancer were enrolled in a prospective study (ESCAPE). PET-MRI was performed: i) before nCRT (tpre); ii) at mid-radiotherapy, tmid; iii) after nCRT, 2-6 weeks before surgery (tpost); nCRT delivered 41.4 Gy/23fr with concurrent carboplatin and paclitaxel. For patients that skipped surgery, complete clinical response (cCR) was assessed if patients showed no local relapse after 18 months; patients with pathological complete response (pCR) or with cCR were considered as complete responders (pCR + cCR). GTV volumes were delineated by two observers (Vpre, Vmid, Vpost) on T2w MRI: ERI and other volume regression parameters at tmid and tpost were tested as predictors of pCR + cCR. RESULTS: Complete data of 25 patients were available at the time of the analysis: 3/25 with complete response at imaging refused surgery and 2/3 were cCR; in total, 10/25 patients showed pCR + cCR (pCR = 8/22). Both ERImid and ERIpost classified pCR + cCR patients, with ERImid showing better performance (AUC:0.78, p = 0.014): A two-variable logistic model combining ERImid and Vpre improved performances (AUC:0.93, p < 0.0001). Inter-observer variability in contouring GTV did not affect the results. CONCLUSIONS: Despite the limited numbers, interim analysis of ESCAPE study suggests ERI as a potential predictor of complete response after nCRT for esophageal cancer. Further validation on larger populations is warranted.

Extended nodal radiotherapy for prostate cancer relapse guided with [11C]-choline PET/CT: ten-year results in patients enrolled in a prospective trial.

AIMS: To report long-term outcomes of relapsed prostate cancer (PC) patients treated in a prospective single-arm study with extended-nodal radiotherapy (ENRT) and [11C]-choline positron emission tomography (PET)/computed tomography (CT)-guided simultaneous integrated boost (SIB) to positive lymph nodes (LNs). METHODS: From 12/2009 to 04/2015, 60 PC patients with biochemical relapse and positive LNs only were treated in this study. ENRT at a median total dose (TD) = 51.8 Gy/28 fr and PET/CT-guided SIB to positive LNs at a median TD = 65.5 Gy was prescribed. Median PSA at relapse was 2.3 (interquartile range, IQR:1.3-4.0) ng/ml. Median number of positive LNs: 2 (range: 1-18). Androgen deprivation therapy (ADT) was prescribed for 48 patients for a median of 30.7 (IQR: 18.5-43.1) months. RESULTS: Median follow-up from the end of salvage treatment was 121.8 (IQR: 116.1, 130.9) months; 3-, 5-, and 10-year BRFS were 45.0%, 36.0%, and 24.0%, respectively; DMFS: 67.9%, 57.2%, and 45.2%; CRFS: 62.9%, 53.9%, and 42.0%; and OS: 88.2%, 76.3%, and 47.9%, respectively. Castration resistance (p < 0.0001) and ≥ 6 positive LN (p = 0.0024) significantly influenced OS at multivariate analysis. Castration resistance (p < 0.0001 for both) influenced DMFS and CRFS in multivariate analysis. CONCLUSIONS: In PC relapsed patients treated with ENRT and [11C]-choline-PET/CT-guided SIB for positive LNs, with 10-year follow-up, a median Kaplan-Meier estimate CRFS of 67 months and OS of 110 months were obtained. These highly favorable results should be confirmed in a prospective, randomized trial.

A multicenter LArge retrospectIve daTabase on the personalization of stereotactic ABlative radiotherapy use in lung metastases from colon-rectal cancer: The LaIT-SABR study.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic disease, but local control of colorectal metastases remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate the progression to the polymetastatic disease (PMD). MATERIAL AND METHODS: The study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1033 lung metastases were reported. Clinical and biological parameters were evaluated as predictive for freedom from local progression-free survival (FLP). Secondary end-point was the time to the polymetastatic conversion (tPMC). RESULTS: Two-year FLP was 75.4%. Two-year FLP for lesions treated with a BED < 00 Gy, 100-124 Gy, and ≥125 Gy was 76.1%, 70.6%, and 94% (p = 0.000). Two-year FLP for lesion measuring ≤10 mm, 10-20 mm, and >20 mm was 79.7%, 77.1%, and 66.6% (p = 0.027). At the multivariate analysis a BED ≥125 Gy significantly reduced the risk of local progression (HR 0.24, 95%CI 0.11-0.51; p = 0.000). Median tPMC was 26.8 months. Lesions treated with BED ≥125 Gy reported a significantly longer tPMC as compared to lower BED. The median tPMC for patients treated to 1, 2-3 or 4-5 simultaneous oligometastases was 28.5, 25.4, and 9.8 months (p = 0.035). CONCLUSION: The present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Predictive factors were identified for treatment personalization.

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.

Skin DVHs predict cutaneous toxicity in Head and Neck Cancer patients treated with Tomotherapy.

PURPOSE: To explore the association between planning skin dose-volume data and acute cutaneous toxicity after Radio-chemotherapy for Head and Neck (HN) cancer patients. METHODS: Seventy HN patients were treated with Helical Tomotherapy (HT) with radical intent (SIB technique: 54/66 Gy to PTV1/PTV2 in 30fr) ±â€¯chemotherapy superficial body layer 2 mm thick (SL2) was delineated on planning CT. CTCAE v4.0 acute skin toxicity data were available. Absolute average Dose-Volume Histograms (DVH) of SL2 were calculated for patients with severe (G3) and severe/moderate (G3/G2) skin acute toxicities. Differences against patients with none/mild toxicity (G0/G1) were analyzed to define the most discriminative regions of SL2 DVH; univariable and multivariable logistic analyses were performed on DVH values, CTV volume, age, sex, chemotherapy. RESULTS: Sixty-one % of patients experienced G2/G3 toxicity (rate of G3 = 19%). Differences in skin DVHs were significant in the range 53-68Gy (p-values: 0.005-0.01). V56/V64 were the most predictive parameters for G2/G3 (OR = 1.12, 95%CI = 1.03-1.21, p = 0.001) and G3 (OR = 1.13, 95%CI = 1.01-1.26, p = 0.027) with best cut-off of 7.7cc and 2.7cc respectively. The logistic model for V56 was well calibrated being both, slope and R2, close to 1. Average V64 were 2.2cc and 6cc for the two groups (G3 vs G0-G2 toxicity); the logistic model for V64 was quite well calibrated, with a slope close to 1 and R2 equal to 0.60. CONCLUSION: SL2 DVH is associated with the risk of acute skin toxicity. Constraining V64 < 3cc (equivalent to a 4x4cm2 skin surface) should keep the risk of G3 toxicity below or around 10%.

Moderate Hypofractionation with Simultaneous Integrated Boost in Prostate Cancer: Long-term Results of a Phase I-II Study.

AIMS: To report 5 year outcome and late toxicity in prostate cancer patients treated with image-guided tomotherapy with a moderate hypofractionated simultaneous integrated boost approach. MATERIALS AND METHODS: In total, 211 prostate cancer patients, 78 low risk, 53 intermediate risk and 80 high risk were treated between 2005 and 2011. Intermediate- and high-risk patients received 51.8 Gy to pelvic lymph nodes and concomitant simultaneous integrated boost to prostate up to 74.2 Gy/28 fractions, whereas low-risk patients were treated to the prostate only with 71.4 Gy/28 fractions. Daily megavoltage computed tomography (MVCT) image guidance was applied. Androgen deprivation was prescribed for a median duration of 6 months for low-risk patients (for downsizing), 12 months for intermediate-risk and 36 months for high-risk patients. The 5 year biochemical relapse-free survival (bRFS), cancer-specific survival (CSS), overall survival and late gastrointestinal and genitourinary CTCAE.v3 toxicity were assessed. The effect of several clinical variables on both outcome and gastrointestinal/genitourinary toxicity was tested by uni- and multivariate Cox regression analyses. RESULTS: After a median follow-up of 5 years, the late toxicity actuarial incidence was: genitourinary ≥ grade 2: 20.2%; genitourinary ≥ grade 3: 5.9%; gastrointestinal ≥ grade 2: 17%; gastrointestinal ≥ grade 3: 6.3% with lower prevalence at the last follow-up visit (≥ grade 3: genitourinary: 1.9%; gastrointestinal: 1.9%). Major predictors of ≥ grade 3 genitourinary and gastrointestinal late toxicity were genitourinary acute toxicity ≥ grade 2 (hazard ratio: 4.9) and previous surgery (hazard ratio: 3.4). The overall 5 year bRFS was 93.7% (low risk: 94.6%; intermediate risk: 96.2%; high risk: 91.1%), overall survival and CSS were 88.6% (low risk: 90.5%; intermediate risk: 87.4%; high risk: 87%) and 97.5% (low risk: 98.7%; intermediate risk: 95%; high risk: 94.3%), respectively. Risk classes and androgen deprivation were not significantly correlated with either bRFS, overall survival or CSS. Twelve patients experienced a biochemical relapse but none experienced clinically proven local and/or pelvic recurrence. CONCLUSION: A satisfactory 5 year outcome with an acceptable toxicity profile was observed. The combination of image-guided radiotherapy-intensity-modulated radiotherapy, high equivalent 2 Gy dose (EQD2) with a moderate hypofractionated approach and extensive prophylactic lymph node irradiation also leads to very good outcome in high-risk patients.

Biological optimization of simultaneous boost on intra-prostatic lesions (DILs): sensitivity to TCP parameters.

The aim of this investigation was to explore the potential of biological optimization in the case of simultaneous integrated boost on intra-prostatic dominant lesions (DIL) and evaluating the impact of TCP parameters uncertainty. Different combination of TCP parameters (TD50 and γ50 in the Poisson-like model), were considered for DILs and the prostate outside DILs (CTV) for 7 intermediate/high-risk prostate patients. The aim was to maximize TCP while constraining NTCPs below 5% for all organs at risk. TCP values were highly depending on the parameters used and ranged between 38.4% and 99.9%; the optimized median physical doses were in the range 94-116 Gy and 69-77 Gy for DIL and CTV respectively. TCP values were correlated with the overlap PTV-rectum and the minimum distance between rectum and DIL. In conclusion, biological optimization for selective dose escalation is feasible and suggests prescribed dose around 90-120 Gy to the DILs. The obtained result is critically depending on the assumptions concerning the higher radioresistence in the DILs. In case of very resistant clonogens into the DIL, it may be difficult to maximize TCP to acceptable levels without violating NTCP constraints.