Hypopharyngeal carcinoma in Finland from 2005 to 2014 : outcome remains poor after major changes in treatment

Purpose Hypopharyngeal carcinoma (HPC) is typically diagnosed at late stages, the patients tend to have serious co-morbidities, distant relapses are frequent, and the related mortality remains high. The treatment paradigm of HPC has remarkably changed from primary surgical approach toward definitive, platinum-based concomitant chemoradiotherapy (CRT). Our aim was to analyze the HPC treatment approaches and outcome in a nationwide series and to make a comparison with a previously published corresponding nationwide patient cohort from the period 1990-1999. Methods We retrospectively reviewed all patients diagnosed with HPC at the five university hospitals in Finland between 2005 and 2014. Results The cohort comprised 231 patients. Treatment with curative intent was offered for 175 (76%) patients and consisted of definitive radiotherapy (RT) or CRT in 156 (89%) patients, while 20 (11%) patients had primary surgery with or without adjuvant RT or CRT. The 5-year estimates for overall survival (OS) and disease specific survival (DSS) for the whole study group were 22.7% and 36.5%, respectively. For patients treated with curative intent, the 5-year estimates for OS and DSS were 29.4% and 44.3%, respectively. Conclusions The treatment approach of HPC in Finland has changed thoroughly, as in the 1990s, 63% of HPC patients with curative treatment intent underwent primary surgery with or without RT, while in the current study, the primary treatment approach was non-surgical in 89% of the patients. However, the survival figures have not changed and remain dismal, but most of the few surviving patients now can retain their larynx.Peer reviewe

Hypopharyngeal carcinoma in Finland from 2005 to 2014: outcome remains poor after major changes in treatment

Purpose Hypopharyngeal carcinoma (HPC) is typically diagnosed at late stages, the patients tend to have serious co-morbidities, distant relapses are frequent, and the related mortality remains high. The treatment paradigm of HPC has remarkably changed from primary surgical approach toward definitive, platinum-based concomitant chemoradiotherapy (CRT). Our aim was to analyze the HPC treatment approaches and outcome in a nationwide series and to make a comparison with a previously published corresponding nationwide patient cohort from the period 1990-1999. Methods We retrospectively reviewed all patients diagnosed with HPC at the five university hospitals in Finland between 2005 and 2014. Results The cohort comprised 231 patients. Treatment with curative intent was offered for 175 (76%) patients and consisted of definitive radiotherapy (RT) or CRT in 156 (89%) patients, while 20 (11%) patients had primary surgery with or without adjuvant RT or CRT. The 5-year estimates for overall survival (OS) and disease specific survival (DSS) for the whole study group were 22.7% and 36.5%, respectively. For patients treated with curative intent, the 5-year estimates for OS and DSS were 29.4% and 44.3%, respectively. Conclusions The treatment approach of HPC in Finland has changed thoroughly, as in the 1990s, 63% of HPC patients with curative treatment intent underwent primary surgery with or without RT, while in the current study, the primary treatment approach was non-surgical in 89% of the patients. However, the survival figures have not changed and remain dismal, but most of the few surviving patients now can retain their larynx.</p

Biweekly Cabazitaxel Is a Safe Treatment Option for Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients After Docetaxel - A Final Analysis of the Prosty II Trial

Background/Aim: Our phase III trial showed that biweekly docetaxel (D) is better tolerated than triweekly D in metastatic castration-resistant prostate cancer (mCRPC). The safety of biweekly cabazitaxel (CBZ) post-docetaxel was studied in mCRPC. Patients and Methods: Altogether, 60 patients received CBZ 16 mg/m2 i.v. on day 1 and day 14 of a 4-week cycle. The mean serum PSA levels were 305 ng/ml, and the mean age 67 years. The primary endpoint was safety according to CTCAEv4.0. Results: A total of 255 4-week cycles of CBZ were administered. The most common grade 3/4 adverse events were neutropenia (16.7%), pain (13.3%), fatigue (10.0%), anemia (5.0%) and non-neutropenic infection (10.0%). PSA responses occurred in 10 patients (16.7%). Clinical benefit rate was 38.3% and median survival 10 months. Conclusion: Biweekly CBZ is a well-tolerated treatment resulting in meaningful benefits for heavily pretreated mCRPC patients.Peer reviewe

Hypopharyngeal carcinoma in Finland from 2005 to 2014 : outcome remains poor after major changes in treatment

Purpose Hypopharyngeal carcinoma (HPC) is typically diagnosed at late stages, the patients tend to have serious co-morbidities, distant relapses are frequent, and the related mortality remains high. The treatment paradigm of HPC has remarkably changed from primary surgical approach toward definitive, platinum-based concomitant chemoradiotherapy (CRT). Our aim was to analyze the HPC treatment approaches and outcome in a nationwide series and to make a comparison with a previously published corresponding nationwide patient cohort from the period 1990-1999. Methods We retrospectively reviewed all patients diagnosed with HPC at the five university hospitals in Finland between 2005 and 2014. Results The cohort comprised 231 patients. Treatment with curative intent was offered for 175 (76%) patients and consisted of definitive radiotherapy (RT) or CRT in 156 (89%) patients, while 20 (11%) patients had primary surgery with or without adjuvant RT or CRT. The 5-year estimates for overall survival (OS) and disease specific survival (DSS) for the whole study group were 22.7% and 36.5%, respectively. For patients treated with curative intent, the 5-year estimates for OS and DSS were 29.4% and 44.3%, respectively. Conclusions The treatment approach of HPC in Finland has changed thoroughly, as in the 1990s, 63% of HPC patients with curative treatment intent underwent primary surgery with or without RT, while in the current study, the primary treatment approach was non-surgical in 89% of the patients. However, the survival figures have not changed and remain dismal, but most of the few surviving patients now can retain their larynx.Peer reviewe

Pim-1 Kinase Expression Predicts Radiation Response in Squamocellular Carcinoma of Head and Neck and Is under the Control of Epidermal Growth Factor Receptor12

Pim-1 is an oncogenic serine/threonine kinase with poorly defined function in epithelial cancers. In this study, we determined 1) associations of Pim-1 expression with clinicopathological parameters including responsiveness to irradiation in squamocellular cancers of head and neck and 2) how Pim-1 expression is controlled subsequent to irradiation. Moderate to high expression of Pim-1 correlated to poor response to radiation therapy (P = .003). It is also associated to the expression of epidermal growth factor receptor (EGFR, P < .0001), which has been shown to be activated by irradiation. In radioresistant tumors, irradiation promoted nuclear translocation of Pim-1 (P < .005). When directly testing EGFR dependence of Pim-1 expression, up-regulation and nuclear translocation of Pim-1 could be induced through stimulation of EGFR with its ligands EGF or transforming growth factor α. Both ligand- and irradiation-induced changes in Pim-1 expression and localization could be inhibited by the monoclonal anti-EGFR antibody cetuximab and by the tyrosine kinase inhibitor gefitinib also targeting EGFR. These results suggest that irradiation-induced activation of EGFR upregulates Pim-1, and Pim-1 may be used as a novel predictive marker of radiation response in patients with squamocellular cancers of head and neck

Effect of docetaxel added to bicalutamide in Hormone-Naïve non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14)

Background: Historically, endocrine therapy was used in a range of scenarios in patients with rising PSA, both as a treatment for locally advanced non-metastatic prostate cancer and PSA recurrence following curative intended therapy. In the present study the objective was to investigate if chemotherapy added to endocrine therapy could improve progression-free survival (PFS). Materials and Methods: Patients with hormone-naïve, non-metastatic prostate cancer and rising prostate-specific antigen (PSA), enrolled from Sweden, Denmark, the Netherlands, and Finland, were randomized to long-term bicalutamide (150 mg daily) or plus docetaxel (75 mg/m2, q3w, 8–10 cycles) without prednisone, after stratification for the site, prior local therapy or not, and PSA doubling time. The primary endpoint was 5-year PFS analyzed with a stratified Cox proportional hazards regression model on intention to treat basis. Results: Between 2009 and 2018, a total of 348 patients were randomized; 315 patients had PSA relapse after radical treatment, 33 patients had no prior local therapy. Median follow-up was 4.9 years (IQR 4.0–5.1). Adding docetaxel improved PFS (HR 0.68, 95% CI 0.50–0.93; p = 0.015). Docetaxel showed an advantage for patients with PSA relapse after prior local therapy (HR 0.67, 95% CI 0.49–0.94; p = 0.019). One event of neutropenic infection/fever occurred in 27% of the patients receiving docetaxel. Limitations were slow recruitment, lack of enrolling patients without radical local treatment, and too short follow-up for evaluation of overall survival in patients with PSA relapse. Conclusion: Docetaxel improved PFS in patients starting bicalutamide due to PSA relapse after local therapy or localized disease without local therapy. Confirmatory studies of the efficacy of docetaxel in the setting of PSA-only relapse in addition to endocrine therapies may be justified if longer follow-up will show increased metastatic-free survival