Ruolo della Tac con perfusione nel predire la risposta tumorale alla radioterapia nei pazienti affetti da neoplasie testa-collo

RIASSUNTO ANALITICO Obiettivo dello studio L’obiettivo primario del nostro studio è stato quello di analizzare in maniera prospettica le variazioni dei valori dei parametri perfusionali tumorali tra il pre e post-trattamento nei pazienti affetti da HNC localmente avanzato sottoposti a radiochemioterapia concomitante esclusiva con intento curativo e di correlarle con la risposta PET/CT post-trattamento. Materiali e metodi Questo studio è stato realizzato grazie alla collaborazione della U.O. di Radioterapia Oncologica Universitaria con le U.O. di Radiodiagnostica Universitaria e Medicina Nucleare Universitaria. Lo studio ha previsto l’arruolamento in maniera prospettica di pazienti con neoplasia in stadio intermedio o localmente avanzato del distretto cervico-cefalico (Stadio II-IV) candidati a trattamento di radioterapia (RT), radiochemioterapia (RTCT) o radioterapia + Cetuximab con intento curativo. Tutti i pazienti arruolati nello studio sono stati sottoposti a stadiazione pre-trattamento mediante una panendoscopia del distretto ORL con biopsia, TC con m.d.c. del distretto ORL e FDG-PET/CT total body. In corso di TC diagnostica-stadiativa è stato effettuato anche lo studio basale della perfusione tumorale limitatamente alla lesione primitiva. Il follow-up ha previsto invece una valutazione precoce della risposta a 3 settimane mediante TC perfusionale e successivamente a 3 mesi dal termine del trattamento mediante TC perfusionale e FDG-PET/CT. Successivamente il follow-up del paziente ha proseguito in maniera routinaria secondo il protocollo del centro (visite ORL a cadenza mensile o trimestrale e TC del distretto testa-collo semestrali per i primi due anni dopodichè visite ORL semestrali e TC annuale). La risposta metabolica PET/CT è stata definita in base ai criteri PERCIST (Positron Emission Respons Criteria in Solid Tumors). La prima valutazione eseguita è stata correlare la variazione dei parametri TC perfusionali (BV, BF, MTT, PS) a tre settimane e a tre mesi dal termine del trattamento radioterapico rispetto al baseline. Successivamente tutte le variabili risultate significative all’analisi di correlazione sono state inserite in un modello lineare generalizzato per determinare il contributo di ogni singolo fattore prognostico al punteggio assegnato alla PET/CT. Risultati Dal Luglio 2012 al Luglio 2014 sono stati arruolati presso il nostro centro 25 pazienti affetti da neoplasia non operata del distretto testa-collo, candidati a trattamento radioterapico esclusivo ad intento radicale, associato o meno a chemioterapia o Cetuximab concomitante. La variazione dei singoli parametri perfusionali tra il baseline ed il post-trattamento è risultata statisticamente significativa per tutti i parametri sia a 3 settimane che a 3 mesi ad eccezione dell’MTT a 3 settimane (p=0,241). Per le successive analisi è stato attribuito un punteggio alla risposta PET/TC (0= risposta completa, 1=risposta parziale, 2=stabilità o progressione di malattia). L’analisi univariata ha mostrato una correlazione significativa tra la variazione di tutti i parametri perfusionali e la risposta PET/CT, tranne che per l’ MTT (p=0,676). Nella successiva analisi multivariata, che è stata eseguita tenendo conto delle sole variabili significative all’univariata, la significatività statistica è stata mantenuta per il solo parametro PS (p=0,037) mentre è stata persa per gli altri due. Per valutare se il valore assoluto dei parametri perfusionali misurato in condizioni basali potesse essere predittivo di risposta PET/CT a tre mesi dal termine del trattamento è stato attribuito alla PET/CT un punteggio dicotomico (0=risposta completa, 1= risposta parziale, stabilità e progressione di malattia). L’analisi ha mostrato una correlazione ai limiti della significatività statistica per il BV e il PS (rispettivamente p= 0.078 e p=0.084), ovvero i pazienti che hanno un elevato valore di questi parametri sembrano avere una maggior probabilità di andare incontro ad una risposta metabolica completa valutata mediante PET/CT. Conclusioni La CTP è una metodica relativamente recente e non ancora validata nell’utilizzo nella pratica clinica quotidiana. I risultati della nostra esperienza preliminare confermano in buona parte quelli già riportati dalle altre esperienze facendo emergere però, in maniera ancora più evidente, il ruolo del parametro PS come possibile fattore predittivo di risposta tumorale. Data l’esiguità campionaria ma soprattutto il breve follow-up della nostra casistica, è stato possibile solo confrontare i risultati della CTP con quelli della PET/CT. Riteniamo invece che un follow-up più lungo ed una maggior numerosità campionaria saranno utili in futuro per capire se il decremento di uno o più parametri perfusionali sia predittivo di un miglior outcome oncologico in termini di recidiva locoregionale e sopravvivenza

Role of perfusion CT in the evaluation of functional primary tumour response after radiochemotherapy in head and neck cancer: Preliminary findings

Objective: To report the initial results of a prospective study aimed at evaluating the CT perfusion parameter changes (ΔPCTp) of the primary tumour after radiochemotherapy (RCT) in head and neck cancer (HNC) and to correlate with positron emission tomography (PET)/CT response. Methods: Eligibility criteria included HNC (Stage III-IV) candidates for RCT. Patients underwent perfusion CT (PCT) at baseline and at 3 weeks and 3 months after treatment. Blood volume, blood flow, mean transit time (MTT) and permeability surface (PS) product were computed. Moreover, PET/CT was performed at baseline and 3 months after treatment. The ΔPCTp were evaluated between baseline and 3-week/3-month evaluations, whereas PET/CT response was based on the maximum standardized uptake value changes according to the European Organization for Research and Treatment of Cancer criteria. Results: Between July 2012 and July 2015, 25 patients were enrolled. A significant reduction of all CT tumour perfusion parameters (PCTp) was observed from the baseline to after RCT (p<0.001). Specifically, a significant reduction was shown at 3 weeks for all PCTp except MTT (from 6.18 to 5.14s; p=0.722). Differently, a significant reduction of all PCTp (p<0.001) including MTT (from 6.18 to 2.24s; p=0.001) was shown at 3 months. Moreover, the reduction of PS resulted in a significant prediction of PET/CT response at 3 months (p=0.037) with the trend also at 3 weeks (p=0.099) at the multivariate analysis. Conclusion: Our preliminary findings seem to show that almost all PCTp are significantly reduced after RCT, whereas PS seems to come out as the strongest factor in predicting the PET/CT response. Advances in knowledge: This article provides information on the potential useful role of PCT in evaluating tumour response after both early and late RCT

[18F]Choline PET/CT and stereotactic body radiotherapy on treatment decision making of oligometastatic prostate cancer patients: Preliminary results

Background: A new entity of patients with recurrent prostate cancer limited to a small number of active metastatic lesions is having growing interest: the oligometastatic patients. Patients with oligometastatic disease could eventually be managed by treating all the active lesions with local therapy, i.e. either surgery or ablative stereotactic body radiotherapy. This study aims to assess the impact of [18F]Choline ([18F]FMCH) PET/CT and the use stereotactic body radiotherapy (SBRT) in patients (pts) with oligometastatic prostate cancer (PCa). Methods: Twenty-nine pts with oligometastatic PCa (≤3 synchronous active lesions detected with [18F]FMCHPET/CT) were treated with repeated salvage SBRT until disease progression (development of > three active synchronous metastases). Primary endpoint was systemic therapy-free survival measured from the baseline [18F]FMCHPET/CT. Results: A total of 45 lesions were treated with SBRT. After a median follow-up of 11.5 months (range 3-40 months), 20 pts were still in the study and did not receive any systemic therapy. Nine pts started systemic therapy, and the median time of the primary endpoint was 39.7 months (CI 12.20-62.14 months). No grade 3 or 4 toxicity was recorded. Conclusions: Repeated salvage [18F]FMCHPET/CT-guided SBRT is well tolerated and could defer the beginning of systemic therapy in selected patients with oligometastatic PCa

Effect of heliox on heart rate kinetics and dynamic hyperinflation during high-intensity exercise in COPD

Respiratory mechanical abnormalities in patients with chronic obstructive pulmonary disease (COPD) may impair cardiodynamic responses and slow down heart rate (HR) kinetics compared with normal resulting in reduced convective oxygen delivery during exercise. We reasoned that heliox breathing (79% helium-21% oxygen) and the attendant reduction of operating lung volumes should accelerate HR kinetics in the transition from rest to high-intensity exercise. Eleven male ambulatory patients with clinically stable COPD undertook constant work-rate cycle testing at 80% of each individuals' maximum work capacity while breathing room air (RA) or heliox (HX), randomly. Mean response time (MRT) for HR and dynamic end-expiratory lung volume (EELV) were measured. Resting EELV was not affected by HX breathing, while exercise EELV decreased significantly by 0.23 L at isotime during HX breathing compared with RA. During FIX breathing, MRT for HR significantly accelerated (p = 0.002) by an average of 20 s (i.e., 17%). Speeded MRT for HR correlated with indices of reduced lung hyperinflation, such as EELV at isotime (r = 0.88, p = 0.03), and with improved exercise endurance time (r = -0.64, p = 0.03). The results confirm that HX-induced reduction of dynamic lung hyperinflation is associated with consistent improvement in indices of cardio-circulatory function such as HR kinetics in the rest-to-exercise transition in COPD patients

Un caso di neoplasia gastrica metastatica trattato con successo con chirurgia e chemioterapia

A case of long-term survivor 50-year-old man treated for advanced gastric cancer with two liver metastases is described. Patient underwent a total gastrectomy with D2 lymphadenectomy and atipic liver resection. After surgery, chemotherapy with PELF achieved a complete clinical response; six month from the fourth cycle, Ca19.9 levels slowly increased until 185 U/mL and a retro-peritoneal lymphadenopathy was detected by US. Three different chemoterapic combinations (FOLFOX, FOLFIRI, FOLFOX4) was administrated but two new liver recurrences spread out. From November 2007 until now, patient received 8 CDF cycles and he obtained a complete clinical response supported by persistent negativity of TC-PET scans. The radiological investigations performed after last admission in our Department for jaundice, revealed multiple liver lesions with Ca19.9 levels of 6.766 U/mL. The patient required placement of metallic biliary endoprosthesis. He is still alive 41 month after primary surgery. We consider this case a successful example of survival increasing by integrated surgery-chemotherapy treatment but also an expression of the failure of current available therapy in the definitive cure for gastric cancer. Metastatic gastric cancer should be considered a disease treatable but not curable

Magnetic Resonance Imaging Derived Biomarkers of {IDH} Mutation Status and Overall Survival in Grade {III} Astrocytomas

The evaluation of the isocitrate dehydrogenase (IDH) mutation status in the glioma decision-making process has diagnostic, prognostic and therapeutic implications. The aim of this study was to evaluate whether conventional magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) can noninvasively predict the most common IDH mutational status (R132H) in GIII-astrocytomas and the overall survival (OS). Hence, twenty-two patients (9-F, 13-M) with a histological diagnosis of GIII-astrocytoma and evaluation of IDH-mutation status (12-wild type, 10-mutant) were retrospectively evaluated. Imaging studies were reviewed for the morphological feature and mean ADC values (ADCm). Statistics included a Fisher\u2019s exact test, Student\u2019s t-test, Spearman\u2019s Test and receiver operating characteristic analysis. A p 64 0.05 value was considered statistically significant for all the tests. A younger age and a frontal location were more likely related to mutational status. IDH-wild type (Wt) exhibited a slight enhancement (p = 0.039). The ADCm values in IDH-mutant (Mut) patients were higher than those of IDH-Wt patients (p < 0.0004). The value of ADC 65 0.99 7 10 123 mm2/s emerged as a \u201ccut-off\u201d to differentiate the mutation state. In the overall group, a positive relationship between the ADCm values and OS was detected (p = 0.003; r = 0.62). Adding quantitative measures of ADC values to conventional MR imaging could be used routinely as a noninvasive marker of specific molecular patterns

Long-Term PSA Control with Repeated Stereotactic Body Radiotherapy in a Patient with Oligometastatic Castration-Resistant Prostate Cancer

Prostate cancer (PCa) is one of the most common malignancies and main causes of cancer death in Western countries. In the presence of metastatic disease, systemic treatment remains the main clinical option. However, since the introduction of highly sensitive imaging techniques, a new clinical 'entity' of metastatic patients with a limited number of lesions has been defined: oligometastatic patients. In this patient group, the use of stereotactic body radiotherapy (SBRT) or other local therapies against all active sites of disease revealed by 18F-choline positron emission tomography/computed tomography (PET/CT) could achieve sufficient prostate-specific antigen (PSA) control. However, a clear benefit of this procedure in terms of significant endpoints is yet to be demonstrated. This case report describes our experience with treating a castration-resistant PCa patient with 18F-choline PET/CT-guided SBRT. Because of the occurrence of 5 metachronous lesions over 4 years, the pattern of recurrence was defined by the local multidisciplinary team as oligometastatic disease, and the patient was treated with 5 courses of SBRT which yielded good PSA control. He started systemic therapy with abiraterone acetate almost 5 years after the diagnosis of recurrent PCa

How does radiotherapy impact swallowing function in nasopharynx and oropharynx cancer? Short -therm results of a prospective study.

The objective of this study is to report the initial results of a prospective trial assessing instrumental deglutition function in nasopharynx and oropharynx cancers after radio or chemoradiotherapy using intensity-modulated radiotherapy (IMRT). IMRT was delivered aiming to spare the swallowing organ at risk (SWOARs) for Stage II-IV naso- and oropharynx cancer. Objective instrumental assessment included videofluoroscopy (VFS), fiberoptic endoscopic evaluation of swallowing (FEES) and oro-pharyngeal-oesophageal scintigraphy (OPES) at baseline and at 1 month after radiotherapy. Dysphagia parameter scores were calculated at each exam after liquid (L) and semi-liquid (SL) bolus intake: pre-deglutition penetration, aspiration, pharyngeal transit time (PTT) and hypopharyngeal retention index (HPRI). Overall, 20 patients (6 nasophaynx and 14 oropharynx) completed treatment and instrumental assessment after 1 month. Comparison between pre- and post-treatment HPRI score values showed a significant worsening in both FEES-L (p = 0.021) and SL (p = 0.02) and at VFS-L (p = 0.008) and SL (p = 0.005). Moreover, a relationship between HPRI worsening at FEES-L and FEES-SL (p = 0.005) as well as at VFS-L and VFS-SL (p 0.2). Only a few patients experienced pre-deglutition penetration (1 patient with base of tongue cancer at FEES-L and SL) and aspiration (1 patient with nasopharynx cancer at OPES-L and FEES-SL) after radiotherapy. Our early results showed that IMRT-SWOARs sparing caused a significant increase in the post-deglutition HPRI score. Longer follow-up will be necessary to evaluate if the increase of HPRI is related to a high risk of developing late aspiration