The predictive role of interim PET after the first chemotherapy cycle and sequential evaluation of response to ABVD in Hodgkin's lymphoma patients-the Polish Lymphoma Research Group (PLRG) Observational Study.

BACKGROUND: Interim PET after two ABVD cycles (iPET2) predicts treatment outcome in classical Hodgkin's lymphoma. To test whether an earlier assessment of chemosensitivity would improve the prediction accuracy, we launched a prospective, multicenter observational study aimed at assessing the predictive value of iPET after one ABVD (iPET1) and the kinetics of response assessed by sequential PET scanning. PATIENTS AND METHODS: Consecutive patients with newly diagnosed classical Hodgkin's lymphoma underwent interim PET scan after one ABVD course (iPET1). PETs were interpreted according to the Deauville score (DS) as negative (-) (DS 1-3) and positive (+) (DS 4, 5). Patients with iPET1 DS 3-5 underwent iPET2. RESULTS: About 106 early (I-IIA) and 204 advanced (IIB-IV) patients were enrolled between January 2008 and October 2014. iPET1 was (-) in 87/106 (82%) or (+) in 19/106 (18%) of early, and (-) in 133/204 (65%) or (+) in 71/204 (35%) of advanced stage patients, respectively. Twenty-four patients were excluded from response analysis due to treatment escalation. After a median follow-up of 38.2 (3.2-90.2) months, 9/102 (9%) early and 43/184 (23%) advanced patients experienced a progression-free survival event. At 36 months, negative and positive predictive value for iPET1 were 94% and 41% (early) and 84% and 43% (advanced), respectively. The kinetics of PET response was assessed in 198 patients with both iPETs. All 116 patients with iPET1(-) remained iPET2(-) (fast responders), 41/82 with IPET1(+) became iPET2(-) (slow responders), and the remaining 41 stayed iPET2(+) (non-responders); progression-free survival at 36 months for fast, slow and non-responders was 0.88, 0.79 and 0.34, respectively. CONCLUSION: The optimal tool to predict ABVD outcome in HL remains iPET2 because it distinguishes responders, whatever their time to response, from non-responders. However, iPET1 identified fast responders with the best outcome and might guide early treatment de-escalation in both early and advanced-stage HL.

Phase I-II study of plitidepsin and dacarbazine as first-line therapy for advanced melanoma.

BACKGROUND: This phase I-II trial compared plitidepsin 1-h infusion alone or combined with dacarbazine (DTIC) 1-h infusion as front-line therapy for advanced melanoma. METHODS: The recommended dose (RD) for plitidepsin/DTIC was defined in the first stage. In the second stage, patients were randomised to receive single-agent plitidepsin 3.2 mg m(-2) (n = 20) on days 1, 8 and 15 every 4 weeks (q4wk) or plitidepsin 2.4 mg m(-2) on days 1, 8 and 15 q4wk combined with DTIC 800 mg m(-2) q4wk (n = 38). RESULTS: The overall response rate with plitidepsin/DTIC was 21.4%; all responders had normal serum lactate dehydrogenase (LDH) levels and performance status ≤ 1 at baseline. Median progression-free survival (PFS) with plitidepsin/DTIC was 3.3 months in all patients, and 4.3 months in those with baseline normal LDH. No responses occurred with single-agent plitidepsin and median PFS was 1.5 months. Both regimens were well tolerated. Haematological abnormalities were more common and transaminase increases more severe with plitidepsin/DTIC. Treatment-related transaminase increases leading to infusion omission on day 8 were relatively common. No drug-drug pharmacokinetic interactions were found. CONCLUSION: This plitidepsin/DTIC schedule has antitumour activity and manageable toxicity in advanced melanoma. Further evaluation of plitidepsin 2.4 mg m(-2) fortnightly and DTIC 800 mg m(-2) q4wk is recommended.

Long-term survival of a patient with primarily chemo-resistant metastatic breast cancer treated with medroxyprogesterone acetate.

The prognosis of breast cancer patients with liver metastases is extremely poor. Here we present the case of a 66-year-old female breast cancer patient with multiple liver metastases diagnosed 2 years after a radical modified mastectomy followed by adjuvant tamoxifen. At progression, anthracycline-based chemotherapy was administered, but a CT scan following two cycles of FEC (5-fluorouracil, epirubicin, cyclophosphamide) showed progression of the liver metastases. Chemotherapy was therefore switched to medroxyprogesterone acetate (MPA). After 3 months the patient's general status improved, and disease stabilization was observed at the next CT scan. A further 4 months of MPA treatment resulted in complete response of all liver lesions. Treatment with oral MPA was continued for 4 years. At present, 11 years after the diagnosis of metastatic liver involvement, the patient is alive, free of cancer, and fully ambulatory. Despite bulky visceral disease and chemoresistance, hormonal treatment with MPA resulted in a spectacular and long-lasting response.

[The value of serum CA 125 for monitoring treatment of patients with ovarian cancer]. / Wartosc oznaczania poziomu CA 125 w surowicy w monitorowaniu leczenia chorych na raka jajnika.

To evaluate the value of serum CA 125 antigen in monitoring of treatment of ovarian carcinoma, serum levels of this marker were monthly assayed during treatment and follow-up period in a group of 112 patients. CA 125 levels decreased in all 67 patients with remission. In a group of 41 patients with progressive disease, in 38 (93%) CA 125 levels increased, and in 3 (7%) - remained elevated. CA 125 became negative in all patients with clinical complete remission, although in 14 (38%) patients in this group second-look laparotomy revealed microscopic disease. In 12 of 15 patients with complete pathologic remission the increase of CA 125 preceded (2 to 58 weeks, median - 12 weeks) the recurrence of the disease. Time to progression depended on the increase rate of the antigen level.

Combination of cisplatin/S-1 in the treatment of patients with advanced gastric or gastroesophageal adenocarcinoma: Results of noninferiority and safety analyses compared with cisplatin/5-fluorouracil in the First-Line Advanced Gastric Cancer Study.

BACKGROUND: The aim of developing oral fluorouracil (5-FU) is to provide a more convenient administration route with similar efficacy and the best achievable tolerance. S-1, a novel oral fluoropyrimidine, was specifically designed to overcome the limitations of intravenous fluoropyrimidine therapies. PATIENTS AND METHODS: A multicentre, randomised phase 3 trial was undertaken to compare S-1/cisplatin (CS) with infusional 5-FU/cisplatin (CF) in 1053 patients with untreated, advanced gastric/gastroesophageal adenocarcinoma. This report discusses a post-hoc noninferiority overall survival (OS) and safety analyses. RESULTS: Results (1029 treated; CS = 521/CF = 508) revealed OS in CS (8.6 months) was statistically noninferior to CF (7.9 months) [hazard ratio (HR) = 0.92 (two-sided 95% confidence interval (CI), 0.80-1.05)] for any margin equal to or greater than 1.05. Statistically significant safety advantages for the CS arm were observed [G3/4 neutropenia (CS, 18.6%; CF, 40.0%), febrile neutropenia (CS, 1.7%; CF, 6.9%), G3/4 stomatitis (CS, 1.3%; CF, 13.6%), diarrhoea (all grades: CS, 29.2%; CF, 38.4%) and renal adverse events (all grades: CS, 18.8%; CF, 33.5%)]. Hand-foot syndrome, infrequently reported, was mainly grade 1/2 in both arms. Treatment-related deaths were significantly lower in the CS arm than the CF arm (2.5% and 4.9%, respectively; P<0.047). CONCLUSION: CS is noninferior to CF with a better safety profile and provides a new treatment option for patients with advanced gastric carcinoma.

[Pigmented villonodular synovitis of the hip. Case report]. / Barwnikowe guzkowo-kosmkowe zapalenie blony maziowej stawu biodrowego. Opis przypadku.

A 35-year woman suffering from the tumor of the right groin for 5 years was diagnosed as a diffuse pigmented villonodular synovitis and tenosynovitis following a 7-month follow-up and examinations. Patient was treated with irradiation which produced a subjective improvement but no significant objective response to the treatment was noted.

[Diagnostic difficulties in the case of a brain tumor of embryonic origin in an 18-year old man]. / Trudnosci diagnostyczne w przypadku guza mózgu pochodzenia zarodkowego u 18-letniego mezczyzny.

A case of an 18-year-old man with symptoms of diabetes insipidus and signs of hypothalamus injury was presented. The computerized tomography of the head and the examination of the cerebrospinal fluid suggested an inflammatory process. After a few-month observation, due to the increased level of tumor markers (human chorionic gonadotropin-HCG) and the results of the MR imaging, a tumor of an embryonic origin was recognized. The type of the tumor is unknown because a biopsy specimen for the histopathology could not have been taken.

CD34 cell dose in granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell grafts affects engraftment kinetics and development of extensive chronic graft-versus-host disease after human leukocyte antigen-identical sibling transplantation.

A retrospective analysis of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cell (G-PBMC) products harvested from healthy donors indicates significant variability in both the absolute number and relative proportion of CD34, CD3, and CD14 cells obtained. This report examined whether variations in the cellular composition of G-PBMC products correlated with clinical outcomes after myeloablative allogeneic transplantation. The numbers of CD34, CD3, and CD14 cells infused into 181 human leukocyte antigen (HLA)-identical sibling recipients were analyzed with respect to tempo of engraftment, acute graft-versus-host-disease (GVHD), clinical extensive chronic GVHD, overall survival, and disease relapse. Neither acute GVHD, overall survival, nor disease relapse was statistically significantly associated with CD34, CD3, or CD14 cell doses or the CD14 to CD3 ratio. CD3 and CD14 cell doses and CD14 to CD3 ratios did not correlate with the tempo of neutrophil and platelet engraftment. However, increasing CD34 cell numbers were significantly associated with accelerated neutrophil (P =.03) and platelet (P =.01) engraftment. Higher doses of CD34 cells (> 8.0 x 10(6)/kg) were also associated with a significantly increased hazard of clinical extensive chronic GVHD (HR = 2.3, 95% confidence interval [CI] 1.4-3.7, P =.001), but neither CD3 nor CD14 doses were statistically significantly associated with chronic GVHD. It was concluded that CD34 cell dose in G-PBMC grafts appears to affect both the engraftment kinetics and the development of clinical extensive chronic GVHD in HLA-identical sibling recipients but without a demonstrable impact on survival, relapse, and acute GVHD. Given the morbidity associated with extensive chronic GVHD, efforts to further accelerate engraftment in HLA-matched sibling transplants by increasing CD34 cell number in G-PBMC products may be counterproductive.