Trends in treatment and overall survival among patients with proximal esophageal cancer

BACKGROUND: The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures. Non-surgical treatment options like radiotherapy and definitive chemoradiation (CRT) have been implemented. The trends in (non-)surgical treatment and its impact on overall survival (OS) in patients with proximal esophageal cancer are unclear, related to its rare disease status. To optimize treatment strategies and counseling of patients with proximal esophageal cancer, it is therefore essential to gain more insight through real-life studies. AIM: To establish trends in treatment and OS in patients with proximal esophageal cancer. METHODS: In this population-based study, patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry. The proximal esophagus consists of the cervical esophagus and the upper thoracic section, extending to 24 cm from the incisors. Trends in radiotherapy, chemotherapy, and surgery, and OS were assessed. Analyses were stratified by presence of distant metastasis. Multivariable Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS, adjusted for patient, tumor, and treatment characteristics. RESULTS: In total, 2783 patients were included. Over the study period, the use of radiotherapy, resection, and CRT in non-metastatic disease changed from 53%, 23%, and 1% in 1989-1994 to 21%, 9%, and 49% in 2010-2014, respectively. In metastatic disease, the use of chemotherapy and radiotherapy increased over time. Median OS of the total population increased from 7.3 mo [95% confidence interval (CI): 6.4-8.1] in 1989-1994 to 9.5 mo (95%CI: 8.1-10.8) in 2010-2014 (logrank P < 0.001). In non-metastatic disease, 5-year OS rates improved from 5% (95%CI: 3%-7%) in 1989-1994 to 13% (95%CI: 9%-17%) in 2010-2014 (logrank P < 0.001). Multivariable regression analysis demonstrated a significant treatment effect over time on survival. In metastatic disease, median OS was 3.8 mo (95%CI: 2.5-5.1) in 1989-1994, and 5.1 mo (95%CI: 4.3-5.9) in 2010-2014 (logrank P = 0.26). CONCLUSION: OS significantly improved in non-metastatic proximal esophageal cancer, likely to be associated with an increased use of CRT. Patterns in metastatic disease did not change significantly over time

A national study to assess outcomes of definitive chemoradiation regimens in proximal esophageal cancer

Background: Proximal esophageal cancer (EC) is commonly treated with definitive chemoradiation (CRT). The radiation dose and type of chemotherapy backbone are still under debate. The objective of this study was to compare the treatment outcomes of contemporary CRT regimens. Material and Methods: In this retrospective observational cohort study, we included patients with locally advanced squamous cell cancer of the proximal esophagus, from 11 centers in the Netherlands, treated with definitive CRT between 2004 and 2014. Each center had a preferential CRT regimen, based on cisplatin (Cis) or carboplatin-paclitaxel (CP) combined with low (≤50.4 Gy) or high (>50.4 Gy) dose radiotherapy (RT). Differences in overall survival (OS) between CRT regimens were assessed using a fully adjusted Cox proportional hazards and propensity score (PS) weighted model. Safety profiles were compared using a multilevel logistic regression model. Results: Two hundred patients were included. Fifty-four, 39, 95, and 12 patients were treated with Cis-low-dose RT, Cis-high-dose RT, CP-low-dose RT, and CP-high-dose RT, respectively. Median follow-up was 62.6 months (95% CI: 47.9–77.2 months). Median OS (21.9 months; 95% CI: 16.9–27.0 months) was comparable between treatment groups (logrank p = .88), confirmed in the fully adjusted and PS weighted model (p > .05). Grades 3–5 acute adverse events were less frequent in patients treated with CP-low-dose RT versus Cis-high-dose RT (OR 3.78; 95% CI: 1.31–10.87; p = .01). The occurrence of grades 3–5 late toxicities was not different between treatment groups. Conclusion: Our study was unable to demonstrate a difference in OS between the CRT regimens, probably related to the relatively small sample size. Based on the superior safety profile, carboplatin and paclitaxel-based CRT regimens are preferred in patients with locally advanced proximal EC

Can localised 19F magnetic resonance spectroscopy pharmacokinetics of 5FU in colorectal metastases predict clinical response?

Background 5-Fluorouracil remains widely used in colorectal cancer treatment more than 40 years after its development. 19F magnetic resonance spectroscopy can be used in vivo to measure 5FU’s half-life and metabolism to cytotoxic fluoronucleotides. Previous studies have shown better survival associated with longer 5FU tumour half-life. This work investigated 5FU pharmacokinetics in liver metastases of colorectal cancer. Methods A total of 32 subjects with colorectal cancer undergoing 5FU treatment, 15 of whom had liver metastases, were examined in a 1.5T MRI scanner, using a large coil positioned over the liver. Non-localised spectra were acquired in 1-min blocks for 32 min after injection of a 5FU bolus. The 5FU half-life was measured in each subject, and averaged spectra were examined for the presence of fluoronucleotides. Associations with progression-free survival were assessed. Results No association was observed between 5FU halflife, tumour burden and survival. Half-lives were all shorter than those associated with improved survival in the literature. Remarkably, in the group with liver metastases, high levels of fluoronucleotides were associated with poorer survival; this counterintuitive result may be due to the higher levels of fluoronucleotides (whose level is higher in tumour tissue than in normal liver) in patients with higher tumour burdens. Conclusions It is recommended that future studies use chemical shift imaging at higher field strengths to better resolve tumour from normal liver. Non-localised spectroscopy retains prognostic potential by enabling straightforward detection of fluoronucleotides, which are present at very low concentrations distributed throughout the tissue

Surgical treatment of acromioclavicular dislocation associated with midshaft fracture of the ipsilateral clavicle

Acromioclavicular dislocation combined with a midshaft clavicle fracture is a rare traumatic shoulder problem. Various treatment options have been described in literature. We describe a new technique using a hook plate and coracoclavicular sling to replace the ruptured coracoclavicular ligaments in combination with plate osteosynthesis of the clavicle fracture. Furthermore, we provide a short overview of the few cases described in literature and their treatment options.

An assisted structured reflection on life events and life goals in advanced cancer patients : Outcomes of a randomized controlled trial (Life InSight Application (LISA) study)

BACKGROUND:: Diagnosis and treatment of incurable cancer as a life-changing experience evokes difficult existential questions. AIM:: A structured reflection could improve patients' quality of life and spiritual well-being. We developed an interview model on life events and ultimate life goals and performed a randomized controlled trial to evaluate the effect thereof on quality of life and spiritual well-being. DESIGN:: The intervention group had two consultations with a spiritual counselor. The control group received care as usual. EORTC QLQ-C15-PAL and the FACIT-sp were administered at baseline and 2 and 4 months after baseline. Linear mixed model analysis was performed to test between-group differences over time. PARTICIPANTS:: Adult patients with incurable cancer and a life expectancy ⩾6 months were randomized in a 1:1 ratio to the intervention or control group. RESULTS:: A total of 153 patients from six different hospitals were included: 77 in the intervention group and 76 in the control group. Quality of life and spiritual well-being did not significantly change over time between groups. The experience of Meaning/Peace was found to significantly influence quality of life ( β = 0.52, adj. R2 = 0.26) and satisfaction with life ( β = 0.61, adj. R2 = 0.37). CONCLUSION:: Although our newly developed interview model was well perceived by patients, we were not able to demonstrate a significant difference in quality of life and spiritual well-being between groups. Future interventions by spiritual counselors aimed at improving quality of life, and spiritual well-being should focus on the provision of sources of meaning and peace

An assisted structured reflection on life events and life goals in advanced cancer patients:Outcomes of a randomized controlled trial (Life InSight Application (LISA) study)

BACKGROUND:: Diagnosis and treatment of incurable cancer as a life-changing experience evokes difficult existential questions. AIM:: A structured reflection could improve patients' quality of life and spiritual well-being. We developed an interview model on life events and ultimate life goals and performed a randomized controlled trial to evaluate the effect thereof on quality of life and spiritual well-being. DESIGN:: The intervention group had two consultations with a spiritual counselor. The control group received care as usual. EORTC QLQ-C15-PAL and the FACIT-sp were administered at baseline and 2 and 4 months after baseline. Linear mixed model analysis was performed to test between-group differences over time. PARTICIPANTS:: Adult patients with incurable cancer and a life expectancy ⩾6 months were randomized in a 1:1 ratio to the intervention or control group. RESULTS:: A total of 153 patients from six different hospitals were included: 77 in the intervention group and 76 in the control group. Quality of life and spiritual well-being did not significantly change over time between groups. The experience of Meaning/Peace was found to significantly influence quality of life ( β = 0.52, adj. R2 = 0.26) and satisfaction with life ( β = 0.61, adj. R2 = 0.37). CONCLUSION:: Although our newly developed interview model was well perceived by patients, we were not able to demonstrate a significant difference in quality of life and spiritual well-being between groups. Future interventions by spiritual counselors aimed at improving quality of life, and spiritual well-being should focus on the provision of sources of meaning and peace