Association between Physical Activity and Menstrual Cycle Disorders in Young Athletes.

Our study aims to evaluate clinical predictors of menstrual cycle disorders in female athletes who compete in running disciplines. This is a prospective observational study. Women were recruited between January and May 2022. Fifty-three patients were enrolled and completed a questionnaire about menstrual cycle, physical activity, and food habit characteristics. Of the women in our population, 39.6% had menstrual irregularities and reported a significantly higher number of kilometers run per week (67 vs. 35, p:0.02). The number of kilometers run per week was associated with menstrual irregularities (for 10 km, OR 1.35; IC95% 1.05-1.73; p: 0.02) after adjusting for BMI, age, level of sport and caloric intake. The variable of "km run per week" appeared as a diagnostic indicator of irregular menstrual cycle with statistical significance (AUC ROC curve 0.71, IC95% 0.54-0.86, p-value=0.01) and the cut-off of 65 km run per week is a good indicator of the presence of irregular menstrual cycle (sensitivity (SE) and specificity (SP) of 55% and 81.48%). Menstrual cycle disorders are very frequent in female athletes, and the variable of km run per week may play a role in screening endurance athletes at high risk for these disorders.

Superinfection of Rectovaginal Endometriosis: Case Report and Review of the Literature.

BACKGROUND: A peculiar complication of endometriosis is a superinfection. However, the superinfection of extra-ovarian endometriosis is anecdotal, and only a few cases have been described. We wanted to present the first cases of the superinfection of rectovaginal endometriosis and to perform a literature review of the superinfection of extra-ovarian endometriosis. METHODS: We present a case of a 24-year-old woman who was referred to our Pelvic Floor Unit for rectal-perineal pain, dyspareunia, and recurrent episodes of dense purulent vaginal discharge for one year, in which the superinfection of rectovaginal endometriosis was diagnosed. Moreover, we performed a systematic search of the literature indexed on PubMed up to 31 January 2023. RESULTS: Laparoscopic drainage was successful in managing this condition. In the literature, clinical presentation and instrumental and microbiological findings are very heterogeneous. However, the gold standard of management is represented by surgical or percutaneous drainage. CONCLUSIONS: In the case of a pelvic abscess, the superinfection of endometriosis lesions should be suspected, and this can represent the onset symptom of endometriosis. Ultrasonography may show nodular or flat hypoechoic lesions with hyperechoic debris and peripheral positive color/power Doppler intensities. The goal of management is to drain the abscess, either percutaneously or via traditional surgery, followed by proper hormonal therapy to reduce recurrence.

Endometriosis-related spontaneous hemoperitoneum in pregnancy: A case series.

Endometriosis can be associated with adverse pregnancy outcomes. We report six cases of endometriosis-related spontaneous hemoperitoneum diagnosed in pregnant and postpartum women over 13 years. Spontaneous hemoperitoneum in pregnancy mainly occurred in the second half of gestation. All women presented with acute abdominal pain; four of them needed an emergent surgery, two were managed expectantly. The median estimated blood loss was 4250 ml, four women required massive transfusion. Three out of six women had a known history of endometriosis, all of them had histologically confirmed endometriosis after surgery. No maternal or perinatal deaths occurred. In one case, reticence to perform a computed tomography scan led to delayed diagnosis. Since delay can lead to lethal consequences, high levels of suspicion for spontaneous hemoperitoneum should be maintained in cases of severe abdominal pain, even with a woman's negative history of endometriosis. Improved knowledge and regular interdisciplinary meetings are pivotal to ameliorate outcomes.

Pelvic pain after laparoscopic lateral suspension for pelvic organ prolapse: an unrecognized problem?

INTRODUCTION AND HYPOTHESIS: The laparoscopic lateral suspension (LLS) represents an alternative mesh procedure to avoid the dissection at the promontory. However, mesh-related complications such as chronic pelvic pain, dyspareunia, and bladder pain are emerging. The present study is aimed to present a video case report and describe a small case series of patients referred to our center for chronic pelvic pain after LLS. METHODS: A surgical video of the management of a 50-year-old woman with chronic abdominal and pelvic pain, dyspareunia, and recurrent urinary tract infection (UTIs) after uterus sparing LLS is provided. Moreover, we performed a retrospective chart review of similar cases in our institution. RESULTS: The featured procedure was completed without complications and was successful in obtaining symptom relief. Between 2018 and 2022 five patients underwent total or subtotal mesh removal for pain-related symptoms after LLS. At the median follow-up of 24 months, all patients were free from pain, but two (40%) required reoperation for prolapse recurrence CONCLUSIONS: Our experience suggests that LLS involves a certain risk of chronic pelvic pain, which may be challenging to manage and require surgical treatment.

Exaggerated mini-puberty in a preterm girl: a case report and review of literature.

OBJECTIVES: Mini-puberty is the physiological and transient activation of the hypothalamic-pituitary-gonadal axis occurring during the first months after birth. In preterm infants, the hormonal surge is more pronounced and longer-lasting than in at-term-peers. To date, only few cases of vaginal bleeding in the setting of an exaggerated mini-puberty have been reported. CASE PRESENTATION: At the corrected age of 3 months, an ex-very-preterm girl presented with breast enlargement and recurrent vaginal bleeding. A remarkable increase in gonadotropins and estradiol levels was detected, while pelvic ultrasound highlighted a large right ovarian cyst. As brain and pituitary MRI showed negative findings, an exaggerated mini-puberty was suspected and no additional investigations were undertaken. The subsequent progressive regression of clinical, biochemical and sonographic findings confirmed the diagnosis. CONCLUSIONS: Although exaggerated mini-puberty of infancy in ex-preterm girls is a rare event, it is important to raise knowledge of this para-physiological condition in order to avoid unnecessary investigations and treatment.

High levels of physical activity in female adolescents with anorexia nervosa: medical and psychopathological correlates.

PURPOSE: While overexercise is commonly described in patients who experience anorexia nervosa (AN), it represents a condition still underestimated, especially in the paediatric population. METHOD: The present study aims at assessing the possible associations between levels of physical activity (PA) and clinical features, endocrinological data and psychopathological traits in a sample of 244 female adolescents hospitalised for AN subdivided into two groups according to PA levels (high PA vs. no/low PA). The two groups were compared through multivariate analyses, while multiple regression analysis was conducted to determine whether physical activity predict specific outcomes. RESULTS: No significant differences were found between the two groups in terms of last Body Mass Index (BMI) before illness, BMI at admission and disease duration, while a difference emerged in delta BMI(rapidity of weight loss), significantly higher in high-PA group (p = 0.021). Significant differences were observed in Free triiodothyronine- (p < 0.001), Free thyroxine (p = 0.046), Follicle-stimulating hormone (p = 0.019), Luteinising hormone (p = 0.002) levels, with values remarkably lower in high-PA group. Concerning psychopathological scales, the high-PA group showed worst Children's Global Assessment Scale (CGAS) scores (p = 0.035). Regression analyses revealed that higher PA predicts higher delta BMI (p = 0.021), presence of amenorrhea (p = 0.003), lower heart rate (p = 0.012), lower thyroid (Free triiodothyronine p < 0.001, Free thyroxine p = 0.029) and gynaecological hormones' levels (Follicle-stimulating hormone p = 0.023, Luteinising hormone p = 0.003, 17-Beta estradiol p = 0.041). Concerning psychiatric measures, HPA predicts worst scores at CGAS (p = 0.019), and at scales for evaluation of alexithymia (p = 0.028) and depression (p = 0.004). CONCLUSIONS: Results suggest that high levels of physical activity in acute AN associate with worst clinical conditions at admission, especially in terms of endocrinological and medical features. LEVEL OF EVIDENCE: Level III.

Stomach and duodenum dose-volume constraints for locally advanced pancreatic cancer patients treated in 15 fractions in combination with chemotherapy.

Purpose: To assess dosimetry predictors of gastric and duodenal toxicities for locally advanced pancreatic cancer (LAPC) patients treated with chemo-radiotherapy in 15 fractions. Methods: Data from 204 LAPC patients treated with induction+concurrent chemotherapy and radiotherapy (44.25 Gy in 15 fractions) were available. Forty-three patients received a simultaneous integrated boost of 48-58 Gy. Gastric/duodenal Common Terminology Criteria for Adverse Events v. 5 (CTCAEv5) Grade ≥2 toxicities were analyzed. Absolute/% duodenal and stomach dose-volume histograms (DVHs) of patients with/without toxicities were compared: the most predictive DVH points were identified, and their association with toxicity was tested in univariate and multivariate logistic regressions together with near-maximum dose (D0.03) and selected clinical variables. Results: Toxicity occurred in 18 patients: 3 duodenal (ulcer and duodenitis) and 10 gastric (ulcer and stomatitis); 5/18 experienced both. At univariate analysis, V44cc (duodenum: p = 0.02, OR = 1.07; stomach: p = 0.01, OR = 1.12) and D0.03 (p = 0.07, OR = 1.19; p = 0.008, OR = 1.12) were found to be the most predictive parameters. Stomach/duodenum V44Gy and stomach D0.03 were confirmed at multivariate analysis and found to be sufficiently robust at internal, bootstrap-based validation; the results regarding duodenum D0.03 were less robust. No clinical variables or %DVH was significantly associated with toxicity. The best duodenum cutoff values were V44Gy < 9.1 cc (and D0.03 < 47.6 Gy); concerning the stomach, they were V44Gy < 2 cc and D0.03 < 45 Gy. The identified predictors showed a high negative predictive value (>94%). Conclusion: In a large cohort treated with hypofractionated radiotherapy for LAPC, the risk of duodenal/gastric toxicities was associated with duodenum/stomach DVH. Constraining duodenum V44Gy < 9.1 cc, stomach V44Gy < 2 cc, and stomach D0.03 < 45 Gy should keep the toxicity rate at approximately or below 5%. The association with duodenum D0.03 was not sufficiently robust due to the limited number of events, although results suggest that a limit of 45-46 Gy should be safe.

Tailoring the radiotherapy approach in patients with anal squamous cell carcinoma based on inguinal sentinel lymph node biopsy.

BACKGROUND AND OBJECTIVES: The aim of our study was to analyze the results of selective inguinal node irradiation in patients with anal cancer, based on the biopsy of the inguinal sentinel lymph node (SLN), in terms of local control and prognosis. METHODS: Records of patients with anal squamous cell carcinoma from January 2001 to December 2016 were retrospectively reviewed. Tc99 lymphoscintigraphy was performed in all the clinically inguinal negative patients, followed by radio-guided surgical removal of the inguinal SLN. All patients were treated with combined radiochemotherapy. In patients with negative sentinel nodes, the inguinal area was excluded in the radiotherapy field. RESULTS: A total of 123 patients, 76 females (61.8%), mean age 60.1 ± 12.19 years old, underwent intraoperative lymph node retrieval. The histological analysis showed metastasis in the SLN in 28 patients (22.8%). The mean follow-up was 43.44 ± 31.86 months. No inguinal recurrence was observed in patients with negative inguinal sentinel node(s). A statistically significant difference was observed for overall and disease-free survivals in a patient with positive and negative inguinal sentinel nodes. CONCLUSIONS: In patients with anal canal cancer, the exclusion of the inguinal regions from the radiotherapy field, in patients with negative SLN, does not compromise locoregional control nor prognosis.

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.

Exploring chemotherapy holiday and drugs re-challenge in advanced pancreatic cancer patients.

PURPOSE: We aimed to explore the role of drugs re-challenge at the disease progression after a chemotherapy-free interval for pancreatic adenocarcinoma (PDAC) patients. METHODS: We retrospectively analyzed the outcome of re-treatments at the progression in two cohorts of advanced PDAC patients who had disease control (DC) and a treatment holiday ≥ 3 months after upfront chemotherapy. RESULTS: Between 2015 and 2019, 66 advanced PDAC patients (cohort A) had DC with nab-paclitaxel-based chemotherapy (i.e. AG or PAXG = cisplatin, nab-paclitaxel, gemcitabine, capecitabine). At the time of progressive disease (PD), 34 patients were re-treated with AG (A1) and 32 were treated with other regimens (A2). The median (m) duration of chemotherapy holiday was 6.1 and 5.9 months in A1 and A2, respectively. Partial response (PR) and stable disease (SD) were found in 14 (41%) and 12 (35%) of patients in A1 and in 8 (25%) and 6 (19%) patients in A2. CA19-9 response was recorded in 23/33 evaluable patients (70%) in A1 and in 5/20 (25%) in A2. mPFS2 and mOS2, defined as the time between the second line of treatment start and the disease progression or death, were 4.8 and 12.2 months in A1 and 3.9 and 8.4 months in A2, respectively. Similarly, between 2006 and 2013, 64 patients (cohort B) had DC with upfront PEFG/PEXG/PDXG regimens (epirubicin or docetaxel, cisplatin, gemcitabine, capecitabine or 5-fluorouracil) and were re-treated at PD with either 4-drug (B1; N = 30) or other regimens (B2; N = 34), yielding a mOS2 of 10.9 and 7.2 months, respectively. CONCLUSION: Our data endorse the strategy of resuming prior drugs after a chemotherapy holiday ≥ 3 months in advanced PDAC patients who achieved a  durable disease control after upfront treatments.

Impact of sentinel lymph-node biopsy and FDG-PET in staging and radiation treatment of anal cancer patients.

To assess the role of sentinel lymph-node biopsy (SLNB) and FDG-PET in staging and radiation treatment (RT) of anal cancer patients. This retrospective study was performed on 80 patients (male: 32, female: 48) with a median age of 60 years (39-89 years) with anal squamous cell carcinoma who were treated from March 2008 to March 2018 at the IRCCS San Raffaele Hospital. Patients without clinical evidence of inguinal LNs metastases and/or with discordance between clinical evidence and imaging features were considered for SLNB. FDG-PET was performed in 69/80 patients. Patients with negative imaging in inguinal region and negative SLNB could avoid RT on groin to spare inguinal toxicity. CTV included GTV (primary tumour and positive LNs) and pelvic ± inguinal LNs. PTV1 and PTV2 corresponded to GTV and CTV, respectively, adding 0.5 cm. RT dose was 50.4 Gy/28 fractions to PTV2 and 64.8 Gy/36 fractions to PTV1, delivered with 3DCRT (n = 24) or IMRT (n = 56), concomitant to Mitomycin-C and 5-FU chemotherapy. FDG-PET showed inguinal uptake in 21/69 patients (30%) and was negative in 48/69 patients (70%). Lymphoscintigraphy was performed in 11/21 positive patients (4 patients SLNB confirmed inguinal metastases, 6 patients false positive and 1 patient SLN not found), and in 29/48 negative patients (5/29 showed metastases, 23/29 true negative and 1 SLN not found). Sensitivity, specificity, positive and negative predictive value of FDG-PET were 62%, 79%, 40% and 82%, respectively. Median follow-up time from diagnosis was 40.3 months (range: 4.6-136.4 months): 69 patients (86%) showed a complete response, 10 patients (13%) a partial response, 1 patient (1%) a stable disease. Patients treated on groin (n = 54) versus not treated (n = 26) showed more inguinal dermatitis (G1-G2: 50% vs. 12%; G3-G4: 17% vs. 0%, p < 0.05). For patients treated on groin, G3-G4 inguinal dermatitis, stomatitis and neutropenia were significantly reduced with IMRT against 3DCRT techniques (13% vs. 36%, p = 0.10; 3% vs. 36%, p = 0.003; 8% vs. 29%, p = 0.02, respectively). SLNB improves the FDG-PET inguinal LNs staging in guiding the decision to treat inguinal nodes. IMRT technique significantly reduced G3-G4 toxicities when patients are treated on groin.

Training and validation of a robust PET radiomic-based index to predict distant-relapse-free-survival after radio-chemotherapy for locally advanced pancreatic cancer.

PURPOSE: To assess the value of 18F-Fluorodeoxyglucose (18F-FDG) PET Radiomic Features (RF) in predicting Distant Relapse Free Survival (DRFS) in patients with Locally AdvancedPancreaticCancer (LAPC) treated with radio-chemotherapy. MATERIALS & METHODS: One-hundred-ninety-eight RFs were extracted using IBSI (Image Biomarker Standardization Initiative) consistent software from pre-radiotherapy images of 176 LAPC patients treated with moderate hypo-fractionation (44.25 Gy, 2.95 Gy/fr). Tumors were segmented by applying a previously validated semi-automatic method. One-hundred-twenty-six RFs were excluded due to poor reproducibility and/or repeatability and/or inter-scanner variability. The original cohort was randomly split into a training (n = 116) and a validation (n = 60) group. Multi-variable Cox regression was applied to the training group, including only independent RFs in the model. The resulting radiomic index was tested in the validation cohort. The impact of selected clinical variables was also investigated. RESULTS: The resulting Cox model included two first order RFs: Center of Mass Shift (COMshift) and 10th Intensity percentile (P10) (p = 0.0005, HR = 2.72, 95%CI = 1.54-4.80), showing worse outcomes for patients with lower COMshift and higher P10. Once stratified by quartile values (highest quartile vs the remaining), the index properly stratified patients according to their DRFS (p = 0.0024, log-rank test). Performances were confirmed in the validation cohort (p = 0.03, HR = 2.53, 95%CI = 0.96-6.65). The addition of clinical factors did not significantly improve the models' performance. CONCLUSIONS: A radiomic-based index including only two robust PET-RFs predicted DRFS of LAPC patients after radio-chemotherapy. The current results could find relevant applications in the treatment personalization of LAPC. A multi-institution independent validation has been planned.

Predicting pathological response after radio-chemotherapy for rectal cancer: Impact of late oxaliplatin administration.

BACKGROUND AND PURPOSE: A previously introduced index based on early tumor (GTV) regression (ERITCP) during neo-adjuvant radio-chemotherapy of rectal cancer was used to investigate the impact of changes of oxaliplatin (OXA) delivery on the prediction of pathological complete response (pCR) and residual vital cell (RVC) fraction. MATERIALS AND METHODS: Ninety-five patients were treated following an adaptive protocol (41.4 Gy/18fr; 2.3 Gy/fr) delivering a simultaneous integrated boost to the residual GTV in the last 6 fractions (3 Gy/fr). OXA was delivered on days -14, 0 (start of RT) and +14. Based on the oncologist's preference, the last OXA cycle was not administered for 36 patients. MRIs taken at planning and at mid-RT were used to calculate ERITCP, before the timing of the third OXA cycle. The impact of OXA cycles and the discriminative power of ERITCP in predicting the pathological response (pCR, RVC >10%) were quantified. Multivariate logistic regression was performed to assess predictive models. RESULTS: Two patients with complete clinical remission refused surgery (cCR_ww). Complete post-surgical data of 54/59 and 35/36 patients were available for the two groups (3 vs 2 OXA cycles). pCR/pCR + cCR_ww/RVC >10% rates were 31.5/33.9/27.8% and 14.3/14.3/54.3% respectively (p = 0.01-0.07). ERITCP showed high negative predictive value (85-91%) for all end-points. The logistic predictive model for pCR included ERITCP (OR: 0.93) and OXA cycles (OR: 3.5), with AUC = 0.78. Internal validation through bootstrap confirmed the robustness of the results. CONCLUSIONS: Late omission of OXA dramatically reduced the pathological response. OXA delivery after the assessment of ERITCP significantly influenced the relationship between ERITCP and pCR.

Surgical management of bladder erosion and pelvic pain after laparoscopic lateral suspension for pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Mesh-augmented lateral suspension for prolapse repair seems to be associated with few complications. However, mesh-related complications can negatively affect the quality of life and may be challenging to manage. This video is aimed at presenting the surgical management of a case of severe pelvic pain and dyspareunia after lateral laparoscopic suspension associated with mesh erosion in the bladder. METHODS: A 46-year-old woman was referred to our Unit for severe pelvic pain and inability to have sexual intercourses since undergoing a uterus-sparing laparoscopic lateral suspension procedure for genital prolapse 2 years before in another hospital. Moreover, she reported bladder pain and recurrent urinary tract infections. Cystoscopy showed mesh erosion in the bladder. She was admitted to laparoscopic hysterectomy plus subtotal mesh excision and bladder reconstruction (video). RESULTS: No surgical complications were observed. The postoperative course was uneventful. At the current follow-up, the patient reported complete resolution of her symptoms. CONCLUSION: The featured video shows laparoscopic subtotal mesh excision, concomitant hysterectomy and bladder repair for pelvic pain, dyspareunia and bladder erosion after lateral suspension. This video may be useful in providing anatomical views and surgical steps necessary for achieving successful surgical management of this mesh-related complication.

Knowledge-based automatic optimization of adaptive early-regression-guided VMAT for rectal cancer.

PURPOSE: To implement a knowledge-based (KB) optimization strategy to our adaptive (ART) early-regression guided boosting technique in neo-adjuvant radio-chemotherapy for rectal cancer. MATERIAL AND METHODS: The protocol consists of a first phase delivering 27.6 Gy to tumor/lymph-nodes (2.3 Gy/fr-PTV1), followed by the ART phase concomitantly delivering 18.6 Gy (3.1 Gy/fr) and 13.8 Gy (2.3 Gy/fr) to the residual tumor (PTVART) and to PTV1 respectively. PTVART is obtained by expanding the residual GTV, as visible on MRI at fraction 9. Forty plans were used to generate a KB-model for the first phase using the RapidPlan tool. Instead of building a new model, a robust strategy scaling the KB-model to the ART phase was applied. Both internal and external validation were performed for both phases: all automatic plans (RP) were compared in terms of OARs/PTVs parameters against the original plans (RA). RESULTS: The resulting automatic plans were generally better than or equivalent to clinical plans. Of note, V30Gy and V40Gy were significantly improved in RP plans for bladder and bowel; gEUD analysis showed improvement for KB-modality for all OARs, up to 3 Gy for the bowel. CONCLUSIONS: The KB-model generated for the first phase was robust and it was also efficiently adapted to the ART phase. The performance of automatically generated plans were slightly better than the corresponding manual plans for both phases.

Early variation of 18-fluorine-labelled fluorodeoxyglucose PET-derived parameters after chemoradiotherapy as predictors of survival in locally advanced pancreatic carcinoma patients.

OBJECTIVE: To investigate if early variation of PET-derived parameters after concomitant chemoradiotherapy (CRT) predicts overall survival (OS), local relapse free survival (LRFS), distant relapse free survival (DRFS) and progression free survival (PFS) in locally advanced pancreatic cancer (LAPC) patients. METHODS: Fifty-two LAPC patients (median age: 61 years; range: 35-85) with available FDG PET/CT before and after RT (2-6 months, median: 2) were enrolled from May 2005 to June 2015. The predictive value of the percentage variation of mean/maximum standard uptake value (ΔSUVmean/max), metabolic tumour volume (ΔMTV) and total lesion glycolysis (ΔTLG), estimated considering different uptake thresholds (40-50-60%), was investigated between pre- and post-RT PET. The percentage difference between gastrointestinal cancer-associated antigen (ΔGICA) levels measured at the time of PET was also considered. Log-rank test and Cox regression analysis were performed to assess the prognostic value of considered PET-derived parameters on survival outcomes. RESULTS: The median follow-up was 13 months (range: 4-130). At univariate analysis, ΔTLG50 showed borderline significance in predicting OS (P = 0.05) and was the most significant parameter correlated to LRFS and PFS (P = 0.001). Median LRFS was 4 and 33 months if ΔTLG50 was below or above 35% respectively (P = 0.0003); similarly, median PFS was 3 vs 6 months (P = 0.0009). No significant correlation was found between PET-derived parameters and DRFS, while the ΔGICA was the only borderline significant prognostic value for this endpoint (P = 0.05). CONCLUSION: PET-derived parameters predict survival in LAPC patients; in particular, ΔTLG50 is the strongest predictor. The combination of these biochemical and imaging biomarkers is promising in identifying patients at higher risk of earlier relapse.

Accurate outcome prediction after neo-adjuvant radio-chemotherapy for rectal cancer based on a TCP-based early regression index.

BACKGROUND AND PURPOSE: An early tumor regression index (ERITCP) was previously introduced and found to predict pathological response after neo-adjuvant radio-chemotherapy of rectal cancer. ERITCP was tested as a potential biomarker in predicting long-term disease-free survival. MATERIALS AND METHODS: Data of 65 patients treated with an early regression-guided adaptive boosting technique (ART) were available. Overall, loco-regional relapse-free and distant metastasis-free survival (OS, LRFS, DMFS) were considered. Patients received 41.4 Gy in 18 fractions (2.3 Gy/fr), including ART concomitant boost on the residual GTV during the last 6 fractions (3 Gy/fr, Dmean: 45.6 Gy). Chemotherapy included oxaliplatin and 5-fluorouracil (5-FU). T2-weighted MRI taken before (MRIpre) and at half therapy (MRIhalf) were available and GTVs were contoured (Vpre, Vhalf). The parameter ERITCP = -ln[(1 - (Vhalf/Vpre))Vpre] was calculated for all patients. Cox regression models were assessed considering several clinical and histological variables. Cox models not including/including ERITCP (CONV_model and REGR_model respectively) were assessed and their discriminative power compared. RESULTS: At a median follow-up of 47 months, OS, LRFS and DMFS were 94%, 95% and 78%. Due to too few events, multivariable analyses focused on DMFS: the resulting CONV_model included pathological complete remission or clinical complete remission followed by surgery refusal (HR: 0.15, p = 0.07) and 5-FU dose >90% (HR: 0.29, p = 0.03) as best predictors, with AUC = 0.75. REGR_model included ERITCP (HR: 1.019, p < 0.0001) and 5-FU dose >90% (HR: 0.18, p = 0.005); AUC was 0.86, significantly higher than CONV_model (p = 0.05). Stratifying patients according to the best cut-off value for ERITCP and to 5-FU dose (> vs <90%) resulted in 47-month DMFS equal to 100%/69%/0% for patients with two/one/zero positive factors respectively (p = 0.0002). ERITCP was also the only variable significantly associated to OS (p = 0.01) and LRFS (p = 0.03). CONCLUSION: ERITCP predicts long-term DMFS after radio-chemotherapy for rectal cancer: an independent impact of the 5-FU dose was also found. This result represents a first step toward application of ERITCP in treatment personalization: additional confirmation on independent cohorts is warranted.

Adjuvant chemoradiation in pancreatic cancer: impact of radiotherapy dose on survival.

BACKGROUND: To evaluate the impact of radiation dose on overall survival (OS) in patients treated with adjuvant chemoradiation (CRT) for pancreatic ductal adenocarcinoma (PDAC). METHODS: A multicenter retrospective analysis on 514 patients with PDAC (T1-4; N0-1; M0) treated with surgical resection with macroscopically negative margins (R0-1) followed by adjuvant CRT was performed. Patients were stratified into 4 groups based on radiotherapy doses (group 1: < 45 Gy, group 2: ≥ 45 and < 50 Gy, group 3: ≥ 50 and < 55 Gy, group 4: ≥ 55 Gy). Adjuvant chemotherapy was prescribed to 141 patients. Survival functions were plotted using the Kaplan-Meier method and compared through the log-rank test. RESULTS: Median follow-up was 35 months (range: 3-120 months). At univariate analysis, a worse OS was recorded in patients with higher preoperative Ca 19.9 levels (≥ 90 U/ml; p < 0.001), higher tumor grade (G3-4, p = 0.004), R1 resection (p = 0.004), higher pT stage (pT3-4, p = 0.002) and positive nodes (p < 0.001). Furthermore, patients receiving increasing doses of CRT showed a significantly improved OS. In groups 1, 2, 3, and 4, median OS was 13.0 months, 21.0 months, 22.0 months, and 28.0 months, respectively (p = 0.004). The significant impact of higher dose was confirmed by multivariate analysis. CONCLUSIONS: Increasing doses of CRT seems to favorably impact on OS in adjuvant setting. The conflicting results of randomized trials on adjuvant CRT in PDAC could be due to < 45 Gy dose generally used.

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.