Fibrosarcomatous transformation represents a rare event in dermatofibrosarcoma protuberans (DFSP) with unpredictable biological behaviour. No guidelines for the adequate treatment of patients with ...this rare neoplasm have been published. Herein, we present a comprehensive review of the literature comprising 157 patients with transformed DFSP focussing on surgical and adjuvant treatment modalities for this tumour. In the cohort examined, local recurrence occurred in 36% of cases and was significantly lower in patients treated by wide excision with margins ≥2 cm when compared with those treated with local excision without defined margins (P = 0.01). Consistently, negative margin status was associated with a lower recurrence rate when compared with positive or unknown margin status (P = 0.01). Distant metastases were detected in 13% of patients, which is significantly higher when compared with ordinary dermatofibrosarcoma protuberans. Systemic dissemination was preceded by local recurrence in 81% of cases, and is therefore strongly associated with tumour recurrence (P ≤ 0.001). The present data confirm that wide excision with margins ≥2 cm represent the gold standard in the treatment of transformed dermatofibrosarcoma protuberans, and prevents recurrence as well as metastasis. When R0‐resection is not feasible, adjuvant radiation should be considered for cases with incomplete resection or unknown surgical margins. Irresectable or metastatic transformed DFSP harbouring the COL1A1‐PDGFB fusion gene should be treated with imatinib in the palliative setting or as an adjunctive treatment before surgery, although responses may be short‐lasting.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The combination of the BCL2 inhibitor venetoclax plus obinutuzumab was more effective in the treatment of older medically ill patients with untreated chronic lymphocytic leukemia than was ...chlorambucil plus obinutuzumab. Progression-free survival at 2 years was 88% with venetoclax and 64% with chlorambucil.
Central venous catheter (CVC)-related bloodstream infections (CRBSI) are a frequent cause of morbidity and mortality in patients with chemotherapy-induced neutropenia. Chlorhexidine containing ...catheter securement dressings may prevent CRBSI.
A multicenter randomized, controlled trial was conducted at 10 German hematology departments. We compared chlorhexidine-containing dressings with non-chlorhexidine control dressings in neutropenic patients. The primary end point was the incidence of definite CRBSI within the first 14 days (dCRBSI14) of CVC placement. Secondary end points included combined incidence of definite or probable CRBSI within 14 days (dpCRBSI14), overall (dpCRBSI), incidence of unscheduled dressing changes and adverse events.
From February 2012 to September 2014, 613 assessable patients were included in the study. The incidence of dCRBSI14 was 2.6% (8/307) in the chlorhexidine and 3.9% (12/306) in the control group (P = 0.375). Both dpCRBSI14 and dpCRBSI were significantly less frequent in the study group with dpCRBSI14 in 6.5% (20/307) of the chlorhexidine group when compared with 11% (34/306) in the control group (P = 0.047), and dpCRBSI in 10.4% (32/307) versus 17% (52/306), respectively (P = 0.019). The frequency of dressing intolerance with cutaneous and soft tissue abnormalities at the contact area was similar in both groups (12.4% and 11.8%; P = 0.901).
Although the trial failed its primary end point, the application of chlorhexidine containing catheter securement dressings reduces the incidence of definite or probable CRBSI in neutropenic patients.
NCT01544686 (Clinicaltrials.gov).
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Patients diagnosed with advanced gastrointestinal stromal tumours (GISTs) who are resistant or intolerant to both imatinib and second-line sunitinib have a poor prognosis and few therapeutic ...options. We evaluated the efficacy of nilotinib, a novel tyrosine kinase inhibitor (TKI) in patients pretreated with imatinib and sunitinib. Fifty-two consecutive patients treated with oral nilotinib, 400 mg twice daily, within the nilotinib compassionate use programme in 12 European cancer centres, were included in this retrospective analysis. Median age was 59 years (range 24–80), and all patients had WHO performance score better than 3. All patients had failed both imatinib and sunitinib pretreatment, either due to progressing GIST (96%) or intolerance (4%). Five patients (10%; 95% confidence interval (CI) 2–18) responded to nilotinib and 19 patients (37%; 95% CI 24–50) achieved a disease stabilisation. Nilotinib was generally well tolerated, but six patients (12%) discontinued treatment due to intolerance. Median progression-free survival of nilotinib treatment was 12 weeks (95% CI 9–15; range 0–104) and median overall survival was 34 weeks (95% CI 3–65; range 2–135). Nilotinib is active in GIST resistant to both imatinib and sunitinib. These results warrant further investigation of nilotinib in GIST.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Richter transformation (RT) is defined as development of aggressive lymphoma in patients (pts) with CLL. The incidence rates of RT among pts with CLL range from 2 to 10%. The aim of this analysis is ...to report the frequency, characteristics and outcomes of pts with RT enrolled in trials of the GCLLSG. A total of 2975 pts with advanced CLL were reviewed for incidence of RT. Clinical, laboratory, and genetic data were pooled. Time-to-event data, starting from time of CLL diagnosis, of first-line therapy or of RT diagnosis, were analyzed by Kaplan-Meier methodology. One hundred and three pts developed RT (3%): 95 pts diffuse large B-cell lymphoma (92%) and eight pts Hodgkin lymphoma (8%). Median observation time was 53 months (interquartile range 38.1-69.5). Median OS from initial CLL diagnosis for pts without RT was 167 months vs 71 months for pts with RT (HR 2.64, CI 2.09-3.33). Median OS after diagnosis of RT was 9 months. Forty-seven pts (46%) received CHOP-like regimens for RT treatment. Three pts subsequently underwent allogeneic and two pts autologous stem cell transplantation. Our findings show that within a large cohort of GCLLSG trial participants, 3% of the pts developed RT after receiving first-line chemo- or chemoimmunotherapy. This dataset confirms the ongoing poor prognosis and high mortality associated with RT.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Patients with CLL responding to initial chemotherapy with fludarabine alone (F) or in combination with cyclophosphamide (FC) were randomized for treatment with alemtuzumab (30 mg i.v. TIW, 12 weeks) ...or observation. Of 21 evaluable patients, 11 were randomized to alemtuzumab before the study was stopped due to severe infections in seven of 11 patients. These infections (one life-threatening pulmonary aspergillosis IV; four CMV reactivations III requiring i.v. ganciclovir; one pulmonary tuberculosis III; one herpes zoster III) were successfully treated and not associated with cumulative dose of alemtuzumab. In the observation arm, one herpes zoster infection II and one sinusitis I were documented. At 6 months after randomization, two patients in the alemtuzumab arm converted to CR, while three patients in the observation arm progressed. After alemtuzumab treatment, five of six patients achieved a molecular remission in peripheral blood while all patients in the observation arm remained MRD-positive (P=0.048). At 21.4 months median follow-up, patients receiving alemtuzumab showed a significant longer progression-free survival (no progression vs mean 24.7 months; P=0.036). In conclusion, a consolidation therapy with alemtuzumab is able to achieve molecular remissions and longer survival in CLL, but a safe treatment regimen needs to be determined.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This study aimed to assess the frequency of and the contributing factors for second primary malignancies (SPMs) and Richter's transformations (RTs) following first-line treatment of chronic ...lymphocytic leukemia within four phase II/III trials of the GCLLSG evaluating fludarabine (F) vs F+cyclophosphamide (FC), chlorambucil vs F, FC without or with rituximab, and bendamustine+R (BR). Among 1458 patients, 239 (16.4%) experienced either an SPM (N=191) or a RT (N=75). Solid tumors (N=115; 43.2% of all second neoplasias) appeared most frequently, followed by RTs (N=75; 28.2%). Patients showed a 1.23-fold increased risk of solid tumors in comparison to the age-matched general population from the German cancer registry. Age>65 (hazard ratio (HR) 2.1; P<0.001), male sex (HR 1.7; P=0.01), co-morbidities (HR 1.6; P=0.01) and number of subsequent treatments⩾1 (HR 12.1; P<0.001) showed an independent adverse prognostic impact on SPM-free survival. Serum thymidine kinase>10 U/l at trial enrollment (HR 3.9; P=0.02), non-response to first-line treatment (HR 3.6; P<0.001) and number of subsequent treatments⩾1 (HR 30.2; P<0.001) were independently associated with increased risk for RT.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background In several studies an increased risk for development of breast cancer, malignant lymphoma and neoplasms of the kidney as second primary cancers in patients with cutaneous melanomas was ...discussed.
Objectives To determine the risk for development of second primary neoplasms in patients with cutaneous melanomas.
Methods A prospective study was performed between 1977 and 1992 to evaluate the occurrence of second primary malignancies in 4597 patients (2083 men, 2514 women) with invasive cutaneous melanomas, diagnosed and treated at the Department of Dermatology and Allergology, Ludwig‐Maximilians‐University, Munich, Germany.
Results During a median follow‐up of 7·2 years, 296 of 4597 patients (6·4%) developed one or more neoplasms at the time of or subsequent to the diagnosis of the first cutaneous melanoma. More than half of these patients developed one or more further melanomas (152, 3·3%). Cancers of the breast, prostate, colon, rectum and kidney occurred less frequently. Statistical calculations revealed a 33·8‐fold increased risk for the development of a second melanoma in the entire group relative risk 38·5 for men (95% CI, 30·4–48·1), 29·0 for women (95% CI, 22·0–37·5). Moreover, a significantly increased risk for the development of kidney carcinoma in men was found relative risk 3·5 (95% CI, 1·4–7·2).
Conclusions Thorough follow‐up and skin examination in patients with cutaneous melanomas is recommended for early detection of other primary melanomas. Furthermore, ultrasound examinations routinely performed in melanoma patients for the detection of melanoma metastases may also be of value for early detection of kidney carcinomas in male patients.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The pharmacological induction of apoptosis in neoplastic B cells presents a promising therapeutic avenue for the treatment of chronic lymphocytic leukemia (CLL). We profiled a panel of clinical ...multi-kinase inhibitors for their ability to induce apoptosis in primary CLL cells. Whereas inhibitors targeting a large number of receptor and intracellular tyrosine kinases including c-KIT, FLT3, BTK and SYK were comparatively inactive, the CDK inhibitors BMS-387032 and flavopiridol showed marked efficacy similar to staurosporine. Using the kinobeads proteomics method, kinase expression profiles and binding profiles of the inhibitors to target protein complexes were quantitatively monitored in CLL cells. The targets most potently affected were CDK9, cyclin T1, AFF3/4 and MLLT1, which may represent four subunits of a deregulated positive transcriptional elongation factor (p-TEFb) complex. Albeit with lower potency, both drugs also bound the basal transcription factor BTF2/TFIIH containing CDK7. Staurosporine and geldanamycin do not affect these targets and thus seem to exhibit a different mechanism of action. The data support a critical role of p-TEFb inhibitors in CLL that supports their future clinical development.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Zusammenfassung
Hintergrund
Wir berichten über das gehäufte Auftreten von Riechstörungen bei COVID-19-Patienten in der ersten Gruppe von COVID-19-Patienten in Deutschland (Webasto-Cluster).
Methode
...Über den Verlust des Geruch- und/oder Geschmackssinns berichteten 26 von 63 COVID-19-Patienten (41 %), wobei nur bei 31 % der von Hyposmie Betroffenen gleichzeitig Symptome einer Rhinitis vorlagen. Bei 14 Patienten führten wir einen Riechtest und bei 10 einen Schmecktest durch. Die Messungen fanden innerhalb der Krankenversorgung einer frühen COVID-19-Kohorte statt.
Ergebnisse
Bei 10/14 Patienten lag sowohl vor als auch nach Abschwellen der Nasenschleimhäute eine Riechstörung vor. Für 2/14 Patienten war die Hyposmie das führende oder sogar das einzige Symptom der SARS-CoV-2-Infektion. Alle Getesteten berichteten über eine Besserung des Geruchs- und/oder Geschmackssinns innerhalb von 8–23 Tagen.
Schlussfolgerung
Den vorliegenden Daten zufolge a) kann COVID-19 bei einer nennenswerten Anzahl Patienten zu Hyposmie führen, die Inzidenz betrug ca. 30 % in dieser Kohorte; b) war die Riechstörung überwiegend nicht mit rhinitischen Symptomen assoziiert, was auf eine nichtrhinitische, z. B. neurogene Ursache hinweisen kann; und c) erholte das Riechvermögen sich weitgehend im Laufe von 1–3 Wochen nach Beginn der COVID-19-Symptome. Anhaltspunkte für ein gehäuftes Auftreten einer Schmeckstörung ergaben sich nicht. Diese frühen Ergebnisse können sowohl bei der Interpretation der COVID-19-assoziierten Hyposmie als auch für ein beruhigendes Patentengespräch angesichts der hier beobachteten temporären Natur der Hyposmie hilfreich sein. Darüber hinaus kann nach derzeitiger Erfahrung eine plötzlich aufgetretene Hyposmie ohne Vorliegen einer neuen Nasenatmungsbehinderung (Rhinitis) das führende oder sogar einzige Symptom einer SARS-CoV-2-Infektion sein.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
PDF
