Longitudinal changes of blood parameters and weight in inoperable stage III NSCLC patients treated with concurrent chemoradiotherapy followed by maintenance treatment with durvalumab.

BACKGROUND: Investigating dynamic changes in blood-parameters and weight in patients with locally advanced non-small cell lung cancer (NSCLC) receiving durvalumab maintenance therapy after chemoradiotherapy (cCRT). Laboratory outcomes were determined based on the number of durvalumab administrations received. METHODS: Twenty-two patients completed platinum-based cCRT followed by maintenance treatment with durvalumab. Different parameters such as hemoglobin (Hb), leukocytes, Lactate dehydrogenase (LDH), C-reactive protein (CRP), body weight and albumin were analyzed before cCRT, after cCRT, 3, 6, 9 and 12 months after starting durvalumab maintenance. RESULTS: Sixteen (72.7%) patients were male; twelve (54.5%) and fifteen (68.2%) patients had non-squamous histology and Union for International Cancer Control (UICC) stage IIIB-C disease, respectively. Median follow-up time was 24.4 months; 12- and 18-months- progression-free and overall-survival rates were 55.0% and 45.0 as well as 90.2 and 85.0%, respectively. During maintenance treatment Hb increased by 1.93 mg/dl (17.53%) after 9 months (p < 0.001) and 2.02 mg/dl (18.46%) after 12 months compared to the start of durvalumab (p < 0.001). LDH decreased by 29.86 U/l (- 11.74%) after 3 months (p = 0.022). Receipt of at least 12 cycles of durvalumab was beneficial in terms of Hb-recovery (Hb 6 months: 12.64 vs. 10.86 [mg/dl]; Hb 9 months: 13.33 vs 11.74 [mg/dl]; (p = 0.03)). Median weight change [kilogram (kg)] was + 6.06% (range: - 8.89 - + 18.75%) after 12 months. The number of durvalumab cycles significantly correlated with total weight gain [kg] (Spearman-Rho-correlation: r = 0.502*). CONCLUSION: In the investigated cohort, no severe hematologic toxicity occurred by laboratory blood tests within 1 year of durvalumab maintenance therapy after cCRT for unresectable stage III NSCLC. Receiving at least 12 cycles of durvalumab appears to have a significant effect on recovery of hemoglobin levels and body weight.

Primary non-small cell lung cancer in a transplanted lung treated with stereotactic body radiation therapy. A case study.

The first case of primary lung cancer in a transplanted lung was described in 2001. Since then, only 5 cases of lung cancer in donated lung have been reported. We present one more patient with non-small cell cancer in the transplanted lung treated with stereotactic body radiation therapy. In most cases of primary lung cancer in transplanted lung, rapid progression of the cancer was reported. Occurrence of the locoregional failure in our case could be explained by factors related to the treatment protocol and also to underlying immunosuppression.

Timing of radiotherapy following breast-conserving surgery: outcome of 1393 patients at a single institution.

BACKGROUND: The role of postoperative radiotherapy in breast-conserving therapy is undisputed. However, optimal timing of adjuvant radiotherapy is an issue of ongoing debate. This retrospective clinical cohort study was performed to investigate the impact of a delay in surgery-radiotherapy intervals on local control and overall survival. PATIENTS AND METHODS: Data from an unselected cohort of 1393 patients treated at a single institution over a 17-year period (1990-2006) were analyzed. Patients were assigned to two groups (CT+/CT-) according to chemotherapy status. A delay in the initiation of radiotherapy was defined as > 7 weeks (CT- group) and > 24 weeks (CT+ group). RESULTS: The 10-year regional recurrence-free survival for the CT- and CT+ groups were 95.6 and 86.0 %, respectively. A significant increase in the median surgery-radiotherapy interval was observed over time (CT- patients: median of 5 weeks in 1990-1992 to a median of 6 weeks in 2005-2006; CT+ patients: median of 5 weeks in 1990-1992 to a median of 21 weeks in 2005-2006). There was no association between a delay in radiotherapy and an increased local recurrence rate (CT- group: p = 0.990 for intervals 0-6 weeks vs. ≥ 7 weeks; CT+ group: p = 0.644 for intervals 0-15 weeks vs. ≥ 24 weeks) or decreased overall survival (CT- group: p = 0.386 for intervals 0-6 weeks vs. ≥ 7 weeks; CT+ group: p = 0.305 for intervals 0-15 weeks vs. ≥ 24 weeks). CONCLUSION: In the present cohort, a delay of radiotherapy was not associated with decreased local control or overall survival in the two groups (CT-/CT+). However, in the absence of randomized evidence, delays in the initiation of radiotherapy should be avoided.

Hippocampus sparing in whole-brain radiotherapy. A review.

Radiation treatment techniques for whole-brain radiation therapy (WBRT) have not changed significantly since development of the procedure. However, the recent development of novel techniques such as intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT) and helical tomotherapy, as well as an increasing body of evidence concerning neural stem cells (NSCs) have altered the conventional WBRT treatment paradigm. In this regard, hippocampus-sparing WBRT is a novel technique that aims to spare critical hippocampus regions without compromising tumour control. Published data on this new technique are limited to planning and feasibility studies; data on patient outcome are still lacking. However, several prospective trials to analyse the feasibility of this technique and to document clinical outcome in terms of reduced neurotoxicity are ongoing.

Chemoradiotherapy duration correlates with overall survival in limited disease SCLC patients with poor initial performance status who successfully completed multimodality treatment.

BACKGROUND AND PURPOSE: Limited data concerning treatment-related prognostic factors in limited disease (LD) small-cell lung cancer (SCLC) patients with poor initial performance status (PS) who successfully completed chemoradiotherapy (CRT) are available. PATIENTS AND METHODS: A total of 125 patients with initial PS WHO 2-3 who successfully completed CRT were retrospectively reviewed. Thoracic radiation therapy (TRT) was applied in the concurrent (group 1) or sequential (group 2) mode. Influence of treatment type, time from diagnosis to start of TRT, number of chemotherapy cycles, prophylactic cranial irradiation (PCI), occurrence of brain metastases (BMs), and duration of CRT on overall survival (OS) were analyzed. RESULTS: Median duration of CRT was 156 days in group 1 and 195 days in group 2 (p < 0.001). Median progression-free survival and OS were 11.6 (95% confidence interval (CI) 10-13.2) and 14.9 (95% CI 11.7-17.6) months with no difference between the groups. The 2- and 3-year survival rates were 37.9 ± 6.9% and 22.7 ± 6.3% in group 1 and 22.4 ± 4.9% and 15.2 ± 4.3% in group 2, respectively. Duration of CRT was only treatment-related factor predicting OS in the uni- (p < 0.014) and multivariate (p < 0.025) analyses. Short dose-dense CRT was associated with improved OS. CONCLUSION: Duration of CRT affects OS in LD SCLC patients with poor initial performance status who successfully completed multimodality treatment.

Translocation of p21(Cip1/WAF1) from the nucleus to the cytoplasm correlates with pancreatic myofibroblast to fibroblast cell conversion.

BACKGROUND AND AIMS: In the pancreas, myofibroblasts (MFBs) were shown to play an important role in the cellular response during inflammation and injury. However, there is only fragmentary information concerning the fate of these cells in pancreas regeneration and fibrosis development. METHODS: Explant cultures of rat pancreatic tissue were used as a model to follow cellular dynamics and phenotype conversion of pancreatic MFBs in vitro. For detailed biochemical analyses a pancreatic fibroblast cell line (long culture fibroblast (LCF)) was generated from MFBs in a long term culture. Cerulein induced acute pancreatitis and dibutyltin dichloride induced pancreas fibrosis were used as experimental models for acute and chronic fibrogenic reactions, respectively. RESULTS: In the explant culture, pancreatic MFBs which derived from fat storing fibroblastic cells underwent apoptosis or converted again to fibroblasts. The phenotype switch to fibroblasts was associated with translocation of p21(Cip1/WAF1) from the nucleus into the cytoplasm. Molecular analyses in LCFs revealed subsequent binding to and inhibition of the activities of Rho kinase 2 and apoptosis signal regulating kinase 1. In the experimentally established pancreas fibrosis, fibroblasts with cytoplasmic expression of p21(Cip1/WAF1) were distributed throughout fibrotic bands whereas in experimental acute pancreatitis MFBs with nuclear expression of p21(Cip1/WAF1) dominated. CONCLUSIONS: The results indicate that pancreatic MFBs are transient and suggest that intracellular localisation of p21(Cip1/WAF1) can contribute to the phenotype conversion of these cells to fibroblasts in culture and experimental injury.