Findings on the efficacy of adjuvant chemotherapy (ACT) of locally advanced cervical cancer (LACC) after the concurrent chemoradiation (CCRT) therapy were inconsistent, and the OUTBACK trial was expected to shed some light regarding the topic. Its results on ACT in LACC were negative, with the conclusion of not to use it. The objective of this review was to present the inconsistencies of previous studies, along with the OUTBACK trial in more detail, and to rethink whether its results provide an unambiguous and definite answer to the optimal position of ACT in the treatment of LACC. To critically appraise the OUTBACK trial and understand the consequences of its results, we used only randomized controlled studies (RCTs) on ACT in LACC that have been included in high-quality systematic reviews and meta-analyses. We calculated the pooled prediction intervals using a random effects meta-analysis of all published randomized studies including the OUTBACK trial. After combining the OUTBACK trial with the results of four previous randomized trials, the pooled hazard ratio for overall survival benefit of CCRT + ACT was 0.95 (95% CI 0.75; 1.20). The pooled hazard ratio of the four previous trials was 1.00 (95% CI 0.69; 1.44). The OUTBACK trial improved the precision of the pooled estimate, but the clinical heterogeneity and the consequent prediction intervals are still very wide, and with 95% reliability, we can expect that if the new study, using a similar approach to the ACT, on a randomly selected patient population from the presented five trials is conducted, its hazard ratio for overall survival after ACT would be between 0.47 and 1.93. In conclusion, there is an absolute need for further research in order to optimally define the position of ACT in the treatment of LACC.

Introduction: Pleural mesothelioma (PM) is a rare neoplasm with median survival time range from 8 to 14 months from diagnosis, and the 5-year survival rate less than 10%, indicating a poor prognosis. The standard treatment for unresectable PM for a long time has been polychemotherapy with pemetrexed and cisplatin for fit patients. Currently, the combination of the anti PD-1 inhibitor nivolumab and the anti-CTLA4 inhibitor ipilimumab has been recognized as the best possible frontline therapy (especially in the sarcomatoid or biphasic type) due to improved outcomes compared to the standard chemotherapy combination. There are still no established predictive biomarkers for any type of systemic therapy in this disease.Case presentation: Patient who presented with cough and dyspnea has been diagnosed with advanced epithelioid type PM in May 2016. He was treated with three lines of therapy, including an antiangiogenic agent and immunotherapy with pembrolizumab in the third line. Immunotherapy with the PD-1 inhibitor pembrolizumab achieved a complete and prolonged response that transferred to long- term survival. Seven years from diagnosis, the patient is still alive. Histological findings showed an unusually immune-inflamed tumor microenvironment possibly leading to excellent response on immunotherapy.Conclusions: The course of the disease in our patient points out that we need better predictive biomarkers to direct the treatment algorithm, as some of the patients, although chemorefractory to the best chemotherapy option, can sustain great benefit of second-line chemotherapy in combination with antiangiogenic agent, and especially immunotherapy, even in late lines of therapy.

Cilj: Ispitati dozimetrijske trendove na organe od rizika i akutnu toksičnost u pacijenata s karcinomom pluća nemalih stanica liječenih trodimenzionalnom konformalnom kemoradioterapijom u jednom onkološkom centru. Metode: Ovo je retrospektivna studija provedena na Klinici za onkologiju i radioterapiju KBC-a Split. Prikupljeni su podatci oboljelih od lokalno uznapredovalog nesitnostaničnog karcinoma pluća liječenih trodimenzionalnom konformalnom radioterapijom od 2011. godine do početka 2019. godine. Prikupljeni su podatci pacijenata koji su se zračili primarno, adjuvantno i/ili neoadjuvantno. Uključeni pacijenti primili su najmanje jedan ciklus kemoterapije. Ciljni volumeni i organi od rizika ocrtani su prema radioterapijskim smjernicama. Rezultati: Medijan doze na “planing treatment volume” bio je 56 Gy. Najčešća akutna radijacijska toksičnost bila je akutni ezofagitis. Nije zabilježen nijedan slučaj akutnog radijacijskog pneumonitisa. Nije pokazana korelacija između prekoračenja doze na zadane volumene organa od rizika i toksičnosti istih, te smo ukazali na trend poboljšanja dozimetrijskih rezultata kroz godine liječenja. Zaključak: Toksičnost liječenja 3D KRT-om lokalno uznapredovalog raka pluća u Klinici za onkologiju i radioterapiju KBC-a Split usporediva je s objavljenim rezultatima drugih svjetskih institucija. S duljim vremenom primjene trodimenzionalne konformalne radioterapije u kliničkoj praksi postiže se optimalna raspodjela doza zračenja na rizične organe.