Integrative Metabolic Signatures for Hepatic Radiation Injury

Background

Radiation-induced liver disease (RILD) is a dose-limiting factor in curative radiation therapy (RT) for liver cancers, making early detection of radiation-associated liver injury absolutely essential for medical intervention. A metabolomic approach was used to determine metabolic signatures that could serve as biomarkers for early detection of RILD in mice.

Methods

Anesthetized C57BL/6 mice received 0, 10 or 50 Gy Whole Liver Irradiation (WLI) and were contrasted to mice, which received 10 Gy whole body irradiation (WBI). Liver and plasma samples were collected at 24 hours after irradiation. The samples were processed using Gas Chromatography/Mass Spectrometry and Liquid Chromatography/Mass Spectrometry.

Results

Twenty four hours after WLI, 407 metabolites were detected in liver samples while 347 metabolites were detected in plasma. Plasma metabolites associated with 50 Gy WLI included several amino acids, purine and pyrimidine metabolites, microbial metabolites, and most prominently bradykinin and 3-indoxyl-sulfate. Liver metabolites associated with 50 Gy WLI included pentose phosphate, purine, and pyrimidine metabolites in liver. Plasma biomarkers in common between WLI and WBI were enriched in microbial metabolites such as 3 indoxyl sulfate, indole-3-lactic acid, phenyllactic acid, pipecolic acid, hippuric acid, and markers of DNA damage such as 2-deoxyuridine. Metabolites associated with tryptophan and indoles may reflect radiation-induced gut microbiome effects. Predominant liver biomarkers in common between WBI and WLI were amino acids, sugars, TCA metabolites (fumarate), fatty acids (lineolate, n-hexadecanoic acid) and DNA damage markers (uridine).

Conclusions

We identified a set of metabolomic markers that may prove useful as plasma biomarkers of RILD and WBI. Pathway analysis also suggested that the unique metabolic changes observed after liver irradiation was an integrative response of the intestine, liver and kidney.     

Postoperative Capecitabine with Concurrent Intensity-Modulated Radiotherapy or Three-Dimensional Conformal Radiotherapy for Patients with Stage II and III Rectal Cancer

Background

The aim of this study was to evaluate the survival outcomes and toxicity of postoperative chemoradiotherapy with capecitabine and concurrent intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT) in patients with stage II and III rectal cancer.

Patients

We recruited 184 patients with pathologically proven, stage II or III rectal cancer. Following total mesorectal excision (TME), the patients were treated with capecitabine and concurrent IMRT/3D-CRT. The treatment regimen consisted of two cycles of oral capecitabine (1600 mg/m²/day), administered twice daily from day 1–14 of radiotherapy, followed by a 7-day rest. The median pelvic dose was 50 Gy in 25 fractions. Oxaliplatin-based adjuvant chemotherapy was administered after the chemoradiotherapy.

Results

The 5-year overall survival, disease-free survival and locoregional control (LRC) rates were 85.1%, 80% and 95.4%, respectively. Grade 3 and 4 toxicities were observed in 28.3% of patients during treatment. Grade 3 or 4 late toxicity, including neurotoxicity or gastrointestinal toxicity, was only observed in nine patients (4.9%).

Conclusions

This study demonstrated that capecitabine chemotherapy with concurrent IMRT/3D-CRT following TME is safe, is well tolerated and achieves superior LRC and favorable survival rates, with acceptable toxicity.     

Prediction of Acute Radiation Mucositis using an Oral Mucosal Dose Surface Model in Carbon Ion Radiotherapy for Head and Neck Tumors

Purpose

To evaluate the dose-response relationship for development of acute radiation mucositis (ARM) using an oral mucosal dose surface model (OMDS-model) in carbon ion radiotherapy (C-ion RT) for head and neck tumors.

Methods

Thirty-nine patients receiving C-ion RT for head and neck cancer were evaluated for ARM (once per week for 6 weeks) according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, and the Radiation Therapy Oncology Group (RTOG) scoring systems. The irradiation schedule typically used was 64 Gy [relative biological effectiveness (RBE)] in 16 fractions for 4 weeks. Maximum point doses in the palate and tongue were compared with ARM in each patient.

Results

The location of the ARM coincided with the high-dose area in the OMDS-model. There was a clear dose-response relationship between maximum point dose and ARM grade assessed using the RTOG criteria but not the CTCAE. The threshold doses for grade 2–3 ARM in the palate and tongue were 43.0 Gy(RBE) and 54.3 Gy(RBE), respectively.

Conclusions

The OMDS-model was useful for predicting the location and severity of ARM. Maximum point doses in the model correlated well with grade 2–3 ARM.     

Risk Factors for Hospital Readmission after Radical Gastrectomy for Gastric Cancer: A Prospective Study

Background

Hospital readmission is gathering increasing attention as a measure of health care quality and a potential cost-saving target. The purpose of this prospective study was to determine risk factors for readmission within 30 days of discharge after gastrectomy for patients with gastric cancer.

Methods

We conducted a prospective study of patients undergoing radical gastrectomy for gastric cancer from October 2013 to November 2014 in our institution. The incidence, cause and risk factors for 30-day readmission were determined.

Results

A total of 376 patients were included in our analysis without loss in follow-up. The 30-day readmission rate after radical gastrectomy for gastric cancer was 7.2% (27of 376). The most common cause for readmission included gastrointestinal complications and postoperative infections. On the basis of multivariate logistic regression analysis, preoperative nutritional risk screening 2002 score ≥ 3 was an independent risk factor for 30-day readmission. Factors not associated with a higher readmission rate included a history of a major postoperative complication during the index hospitalization, prolonged primary length of hospital stay after surgery, a history of previous abdominal surgery, advanced age, body mass index, pre-existing cardiopulmonary comorbidities, American Society of Anesthesiology grade, type of resection, extent of node dissection and discharge disposition.

Conclusions

Readmission within 30 days of discharge after radical gastrectomy for gastric cancer is common. Patients with nutritional risk preoperatively are at high risk for 30-day readmission. Preoperative optimization of nutritional status of patients at nutritional risk may effectively decrease readmission rates.     

The Evaluation of the Risk Factors for Non-Muscle Invasive Bladder Cancer (NMIBC) Recurrence after Transurethral Resection (TURBt) in Chinese Population

Objective

The risk factors of bladder cancer recurrence after transurethral resection of bladder tumor (TURBt) were poorly understood, especially in Chinese population. This study evaluated the potential risk factors of recurrence based on a Chinese population.

Materials and Methods

A total of 698 patients that received TURBt procedure in our institute from 2000 to 2012 were recruited in this study. Clinical information was collected. The patients were followed up according to the schedule recommended by Chinese guideline.

Results

A total of 583 males (83.5%) and 115 females (16.5%) were enrolled in our study. The median follow-up duration was 51.5 months. Gender, chief complain, tumor size, number of lesions, histological grade and chemotherapeutic agents were found significantly associated with patients’ short-term recurrence (less than 1 year) (All p<0.05). In the multivariate analysis, tumor size, number of lesions, histological grade and chemotherapeutic agents were significantly related to patients’ short-term recurrence (less than 1 year) (All p<0.05). A multivariate model based on tumor size, number of lesions, histological grade and chemotherapeutic agents had an AUC of 0.697, which significantly improved the prediction utility for bladder cancer short-term recurrence (less than 1 year) than any single factor In the multivariate Cox regression, tumor size greater than 3 cm, multifocal lesions, worsen histological grade and non-urothelial carcinoma was related to time to recurrence (TR).

Conclusion

Patients with larger tumor size, multifocal number of lesions, higher tumor grade and who received chemotherapeutic agents other than Epirubicin and Pirarubicin might have higher risks of recurrence less than 1 year. Tumor size, number of lesions, pathology and histological grade might be associated with TR. As Bacille Calmette-Guerin (BCG) is currently not approved for bladder cancer in China, Epirubicin and Pirarubicin might be considered prior to other chemotherapy medications when providing post-operative instillation of chemotherapy.     

Warm Ischemic Injury Is Reflected in the Release of Injury Markers during Cold Preservation of the Human Liver

Background

Liver transplantation plays a pivotal role in the treatment of patients with end-stage liver disease. Despite excellent outcomes, the field is strained by a severe shortage of viable liver grafts. To meet high demands, attempts are made to increase the use of suboptimal livers by both pretransplant recovery and assessment of donor livers. Here we aim to assess hepatic injury in the measurement of routine markers in the post-ischemic flush effluent of discarded human liver with a wide warm ischemic range.

Methods

Six human livers discarded for transplantation with variable warm and cold ischemia times were flushed at the end of preservation. The liver grafts were flushed with NaCl or Lactated Ringer’s, 2 L through the portal vein and 1 L through the hepatic artery. The vena caval effluent was sampled and analyzed for biochemical markers of injury; lactate dehydrogenase (LDH), alanine transaminase (ALT), and alkaline phosphatase (ALP). Liver tissue biopsies were analyzed for ATP content and histologically (H&E) examined.

Results

The duration of warm ischemia in the six livers correlated significantly to the concentration of LDH, ALT, and ALP in the effluent from the portal vein flush. No correlation was found with cold ischemia time. Tissue ATP content at the end of preservation correlated very strongly with the concentration of ALP in the arterial effluent (P<0.0007, R² = 0.96).

Conclusion

Biochemical injury markers released during the cold preservation period were reflective of the duration of warm ischemic injury sustained prior to release of the markers, as well as the hepatic energy status. As such, assessment of the flush effluent at the end of cold preservation may be a useful tool in evaluating suboptimal livers prior to transplantation, particularly in situations with undeterminable ischemic durations.     

Evidence based radiation oncology with existing technology

Aim

To assess the real contribution of modern radiation therapy (RT) technology in the more common tumoral types in Central America, Caribbean and South America.

Background

RT is an essential tool in the management of cancer. RT can be either palliative or of curative intent. In general, for palliative radiotherapy, major technologies are not needed.

Materials and methods

We analyzed the contribution of RT technology based on published evidence for breast, lung, gastric, gallbladder, colorectal, prostate and cervix cancer in terms of disease control, survival or toxicity with especial focus on Latin America.

Results

Findings indicate that three dimensional conformal radiation therapy (3D RT) is the gold standard in most common type of cancer in the studied regions. Prostate cancer is probably the pathology that has more benefits when using new RT technology such as intensity modulated radiation therapy (IMRT) versus 3DRT in terms of toxicity and biochemical progression-free survival.

Conclusions

In light of the changes in technology, the ever-increasing access of developing countries to such technology, and its current coverage in Latin America, any efforts in this area should be aimed at improving the quality of the radiotherapy departments and centers that are already in place.     

Evaluating Variations of Bladder Volume Using an Ultrasound Scanner in Rectal Cancer Patients during Chemoradiation: Is Protocol-Based Full Bladder Maintenance Using a Bladder Scanner Useful to Maintain the Bladder Volume?

Purpose

The maintenance of full bladder is important to reduce radiation-induced toxicities and maintain the therapeutic consistency in locally advanced rectal cancer patients who underwent radiotherapy (RT). So, the aim of this study was to evaluate the effectiveness of protocol-based full bladder maintenance by assessing bladder volume variation using an ultrasound bladder scanner to maintain bladder volume.

Materials and Methods

From March 2011 to May 2011, twenty consecutive rectal cancer patients receiving external beam RT participated in this prospective study. Protocol-based full bladder maintenance consisted of education, training and continuous biofeedback by measuring bladder volume. Bladder volume was measured by bladder scan immediately before simulation CT scan and before each treatment three times weekly during the RT period. The relative bladder volume change was calculated. Intra-patient bladder volume variations were quantified using interquartile range (IQR) of relative bladder volume change in each patient. We compared intra-patient bladder volume variations obtained (n=20) with data from our previous study patients (n=20) performing self-controlled maintenance without protocol.

Results

Bladder volumes measured by bladder scan highly correlated with those on simulation CT scan (R=0.87, p<0.001). Patients from this study showed lower median IQR of relative bladder volume change compared to patients of self-controlled maintenance from our previous study, although it was not statistically significant (median 32.56% vs. 42.19%, p=0.058). Upon logistic regression, the IQR of relative bladder volume change was significantly related to protocol-based maintenance [relative risk 1.045, 95% confidence intervals (CI) 1.004-1.087, p=0.033]. Protocol-based maintenance included significantly more patients with an IQR of relative bladder volume change less than 37% than self-controlled maintenance (p=0.025).

Conclusion

Our findings show that bladder volume could be maintained more consistently during RT by protocol-based management using a bladder scan.     

Quality of Life after Post-Prostatectomy Intensity Modulated Radiation Therapy: Pelvic Nodal Irradiation Is Not Associated with Worse Bladder,Bowel, or Sexual Outcomes

Background

Limited data exist regarding toxicity and quality of life (QOL) after post-prostatectomy intensity modulated radiation therapy (IMRT) and whether pelvic nodal RT influences these outcomes.

Methods

118 men were treated with curative-intent RT after radical prostatectomy. 69 men (58%) received pelvic nodal RT. QOL data and physician-assigned toxicity were prospectively collected. Changes in QOL from baseline were assessed with Wilcoxon signed-rank tests and risk factors associated with each domain were identified with generalized estimating equation (GEE) models. Late freedom from (FF) toxicity was estimated by the Kaplan-Meier method and comparisons were tested using the log-rank test.

Results

Urinary irritation/obstruction, bowel, and sexual domain scores declined at 2 months (all P ≤ 0.01) but were no different than baseline at subsequent visits through 4 years of follow-up. At 4 years, FF grade 2+ GI toxicity was 90% and FF grade 2+ GU toxicity was 89%. On GEE analysis, pelvic nodal RT was associated with decreased bowel function (P = 0.09) and sexual function (P = 0.01). On multivariate analysis, however, there was no significant association with either decreased bowel (P = 0.31) or sexual (P = 0.84) function. There was also no association with either FF grade 2+ GI toxicity (P = 0.24) or grade 2+ GU toxicity (P = 0.51).

Conclusions

Receipt of pelvic nodal RT was not associated with inferior QOL or toxicity compared to prostate bed alone RT. For the entire cohort, RT was associated with only temporary declines in patient-reported urinary, bowel, or sexual QOL.     

Fish Intake and Risk of Liver Cancer: A Meta-Analysis

Background

Increasing laboratory findings indicate that n-3 fatty acids, mainly derived from fish, inhibit cancer development and progression, but results from epidemiologic studies have been inconsistent and inconclusive.

Objective

To evaluate the association of fish intake with risk of liver cancer by conducting a meta-analysis.

Methods

Published case-control/cohort studies that evaluated the relationship between total fish intake and risk of liver cancer were found on PubMed and EMBASE. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were obtained with the random-effects model.

Results

Five retrospective case-control studies and 5 prospective cohort studies were included in the final analysis, involving a total of 3 624 liver cancer cases. Comparing the highest with the lowest category of total fish intake, the pooled RRs of liver cancer were 0.79 (95% CI, 0.59-1.06) for case-control studies, 0.82 (95% CI, 0.70-0.96) for cohort studies and 0.82 (95% CI, 0.71-0.94) for all studies combined. The protective effects of total fish intake against liver cancer were confirmed by stratified and sensitivity analyses. In addition, an increase in fish intake of 1 serving/week was estimated to be significantly associated with 6% lower risk of liver cancer (RR = 0.94, 95% CI, 0.91-0.98).

Conclusions

Findings from this meta-analysis suggest that a higher fish intake is associated with reduced risk of liver cancer.     

Synergistic Effect of Anti-Angiogenic and Radiation Therapy: Quantitative Evaluation with Dynamic Contrast Enhanced MR Imaging

Purpose

We assessed the effects of anti-angiogenic therapy (AAT) on radiation therapy (RT), evaluating the tumor growth and perfusion patterns on dynamic contrast enhanced MR (DCE-MR) images.

Methods

Thirteen nude mice with heterotopic xenograft cancer of human lung cancer cell line were used. To observe the interval change of the tumor size and demonstrate the time-signal intensity enhancement curve of the tumor, the mice were subdivided into four groups: control (n = 2), AAT (n = 2), RT (n = 5), and combined therapy (AART, n = 4). DCE-MR images were taken four weeks after treatment. Perfusion parameters were obtained based on the Brix model. To compare the interval size changes in the RT group with those in the AART group, repeated measures ANOVA was used. Perfusion parameters in both the RT and AART groups were compared using a Mann-Whitney U test.

Results

Tumor growth was more suppressed in AART group than in the other groups. Control group showed the rapid wash-in and wash-out pattern on DCE-MR images. In contrast to RT group with delayed and prolonged enhancement, both AAT and AART groups showed the rapid wash-in and plateau pattern. The signal intensity in the plateau/time to peak enhancement (P<0.016) and the maximum enhancement ratio (P<0.016) of AART group were higher than those of RT group.

Conclusions

AART showed synergistic effects in anticancer treatment. The pattern of the time-intensity curve on the DCE-MR images in each group implies that AAT might help maintain the perfusion in the cancer of AART group.     

Causal Effects of Time-Dependent Treatments in Older Patients with Non-Small Cell Lung Cancer

Background

Treatment selection for elderly patients with lung cancer must balance the benefits of curative/life-prolonging therapy and the risks of increased mortality due to comorbidities. Lung cancer trials generally exclude patients with comorbidities and current treatment guidelines do not specifically consider comorbidities, so treatment decisions are usually made on subjective individual-case basis.

Methods

Impacts of surgery, radiation, and chemotherapy mono-treatment as well as combined chemo/radiation on one-year overall survival (compared to no-treatment) are studied for stage-specific lung cancer in 65+ y.o. patients. Methods of causal inference such as propensity score with inverse probability weighting (IPW) for time-independent and marginal structural model (MSM) for time-dependent treatments are applied to SEER-Medicare data considering the presence of comorbid diseases.

Results

122,822 patients with stage I (26.8%), II (4.5%), IIIa (11.5%), IIIb (19.9%), and IV (37.4%) lung cancer were selected. Younger age, smaller tumor size, and fewer baseline comorbidities predict better survival. Impacts of radio- and chemotherapy increased and impact of surgery decreased with more advanced cancer stages. The effects of all therapies became weaker after adjustment for selection bias, however, the changes in the effects were minor likely due to the weak selection bias or incompleteness of the list of predictors that impacted treatment choice. MSM provides more realistic estimates of treatment effects than the IPW approach for time-independent treatment.

Conclusions

Causal inference methods provide substantive results on treatment choice and survival of older lung cancer patients with realistic expectations of potential benefits of specific treatments. Applications of these models to specific subsets of patients can aid in the development of practical guidelines that help optimize lung cancer treatment based on individual patient characteristics.     

The Response,Outcome and Toxicity of Aggressive Palliative Thoracic Radiotherapy for Metastatic Non-Small Cell Lung Cancer Patients with Controlled Extrathoracic Diseases

Background and Purpose

For metastatic non-small cell lung cancer (NSCLC) patients with controlled extrathoracic disease after systemic treatment, stable or progressive primary lung lesions may cause respiratory symptoms and increase comorbidities. In the present study, we sought to investigate whether aggressive palliative thoracic radiotherapy (RT) can enhance local control and improve the survival for this subgroup of patients.

Materials and Methods

Between March 2006 and December 2014, 56 patients with metastatic NSCLC who had responsive or stable extrathoracic diseases after chemotherapy and/or molecular targets, and received thoracic RT for stable and progressive primary lung lesions were included. RT with a median dose of 55 Gy (range, 40–62 Gy) was administered in 1.8–2.5 Gy fractions to primary lung tumor and regional mediastinal lymph nodes using modern RT technique. Overall survival (OS) from diagnosis, and locoregional progression-free survival (LRPFS), and survival calculated from radiotherapy (OS-RT) were estimated using the Kaplan-Meier method.

Results

There were 37 men and 19 women with a median age of 60 years at diagnosis. The median interval from the diagnosis of metastatic disease to thoracic RT was 8 months. Following thoracic RT, 26 patients (46%) achieved complete or partial response (overall response rate, ORR). Patients with squamous cell carcinoma or poorly-differentiated carcinoma had a higher ORR than those with adenocarcinoma (63% vs. 34%, P = 0.034). EGFR mutations was closely associated with a better ORR (45% vs. 29%, P = 0.284). At a median follow-up time of 44 months, the median OS, LRPFS after RT, and OS-RT were 50 months, 15 months, and 18 months.

Conclusion

Radical palliative throractic RT is safe and might be beneficial for primary lung lesions of metastatic NSCLC patients with controlled extrathoracic diseases.     

The Association of Statin Use after Cancer Diagnosis with Survival in Pancreatic Cancer Patients: A SEER-Medicare Analysis

Background

Pancreatic cancer has poor prognosis and existing interventions provide a modest benefit. Statin has anti-cancer properties that might enhance survival in pancreatic cancer patients. We sought to determine whether statin treatment after cancer diagnosis is associated with longer survival in those with pancreatic ductal adenocarcinoma (PDAC).

Methods

We analyzed data on 7813 elderly patients with PDAC using the linked Surveillance, Epidemiology, and End Results (SEER) - Medicare claims files. Information on the type, intensity and duration of statin use after cancer diagnosis was extracted from Medicare Part D. We treated statin as a time-dependent variable in a Cox regression model to determine the association with overall survival adjusting for follow-up, age, sex, race, neighborhood income, stage, grade, tumor size, pancreatectomy, chemotherapy, radiation, obesity, dyslipidemia, diabetes, chronic pancreatitis and chronic obstructive pulmonary disease (COPD).

Results

Overall, statin use after cancer diagnosis was not significantly associated with survival when all PDAC patients were considered (HR = 0.94, 95%CI 0.89, 1.01). However, statin use after cancer diagnosis was associated with a 21% reduced hazard of death (Hazard ratio = 0.79, 95% confidence interval (CI) 0.67, 0.93) in those with grade I or II PDAC and to a similar extent in those who had undergone a pancreatectomy, in those with chronic pancreatitis and in those who had not been treated with statin prior to cancer diagnosis.

Conclusions

We found that statin treatment after cancer diagnosis is associated with enhanced survival in patients with low-grade, resectable PDAC.     

Isoalantolactone Enhances the Radiosensitivity of UMSCC-10A Cells via Specific Inhibition of Erk1/2 Phosphorylation

Background

Although radiotherapy is one of the mainstream approaches for the treatment of head and neck squamous cell carcinoma (HNSCC), this cancer is always associated with resistance to radiation. In this study, the mechanism of action of isoalantolactone as well as its radiosensitizing effect was investigated in UMSCC-10A cells.

Methods

The radiosensitization of UMSCC-10A cells treated with isoalantolactone was analyzed by colony formation assay. The radiosensitization effects of isoalantolactone on cell proliferation, cell cycle and apoptosis regulation were examined by BrdU incorporation assay, DNA content assay and flow cytometry, respectively. Western blotting was performed to determine the effects of isoalantolactone combined with radiation on the protein expression of Mek, extracellular signal-regulated kinase (Erk1/2) as well as phosphorylated Mek and Erk1/2. Erk1/2 knockdown by siRNA was used to confirm that isoalantolactone specifically inhibited the activation of Erk1/2 signaling pathway in UMSCC-10A cells.

Results

Isoalantolactone enhanced the radiosensitivity of UMSCC-10A cells; the sensitivity enhanced ratios (SERs) were 1.44 and 1.63, respectively, for 2.5 and 5 μM. Moreover, isoalantolactone enhanced radiation-induced cell proliferation and apoptosis and cell cycle arrested at G2/M phase. Furthermore, no marked changes were observed in the expression of total Erk1/2 and Mek protein after radiation treatment. However, isoalantolactone was significantly reduced radiation-induced the phosphorylation of Erk1/2, whereas it altered the phosphorylation of Mek to a lesser extent. In addition, the radiosensitivity of UMSCC-10A cells with Erk1/2 knockdown was increased. Isoalantolactone cannot further prevent the proliferation of UMSCC-10A cells with Erk1/2 knockdown which other mechanism regulated cell proliferation.

Conclusion

Our results suggested that isoalantolactone enhanced radiation-induced apoptosis, cell cycle arrested and reduced the cell proliferation of UMSCC-10A cells via specifically inhibited the phosphorylation of Erk1/2. Thus a low concentration of isoalantolactone may be used to overcome the resistance of UMSCC-10A cells to radiation and may be a promising radiosensitizer in cancer therapy.     

Lhermitte’s Sign following VMAT-Based Head and Neck Radiation-Insights into Mechanism

Purpose/Objectives

We observed a number of patients who developed Lhermitte’s sign (LS) following radiation to the head and neck (H/N), since instituting volumetric modulated arc therapy (VMAT). We aimed to investigate the incidence of LS following VMAT-based RT without chemotherapy, and determine the dosimetric parameters that predict its development. We explored whether the role of inhomogeneous dose distribution across the spinal cord, causing a “bath-and-shower” effect, explains this finding.

Methods and Materials

From 1/20/2010–12/9/2013, we identified 33 consecutive patients receiving adjuvant RT using VMAT to the H/N without chemotherapy at our institution. Patients’ treatment plans were analyzed for dosimetric parameters, including dose gradients along the anterior, posterior, right, and left quadrants at each cervical spine level. Institutional Review Board approval was obtained.

Results

5 out of 33 (15.2%) patients developed LS in our patient group, all of whom had RT to the ipsilateral neck only. LS patients had a steeper dose gradient between left and right quadrants across all cervical spine levels (repeated-measures ANOVA, p = 0.030). Within the unilateral treatment group, LS patients received a higher mean dose across all seven cervical spinal levels (repeated-measures ANOVA, p = 0.046). Dose gradients in the anterior-posterior direction and mean doses to the cord were not significant between LS and non-LS patients.

Conclusions

Dose gradients along the axial plane of the spinal cord may contribute to LS development; however, a threshold dose within the high dose region of the cord may still be required. This is the first clinical study to suggest that inhomogeneous dose distributions in the cord may be relevant in humans. Further investigation is warranted to determine treatment-planning parameters associated with development of LS.     

Radiation therapy in the last month of life

Aim

We sought to survey a large, multi-center patient sample to better characterize/quantify RT utilization at the end of life.

Background

Few objective data exist for radiation therapy (RT) delivery at end of life (EOL).

Materials and methods

Data were retrieved for all patients receiving RT in calendar year 2010 in the Department of Radiation Oncology at Indiana University (IU) and Howard University (HU) hospitals. Specific attention was made of the group of patients receiving RT in the last 30 days of life.

Results

A total of 852 patients received all or part of their RT during 2010 (HU: 139, IU: 713). At time of analysis in early 2012, 179 patients had died (21%). Fifty-four patients (6.3% of total; 30% of expired patients) died within 30 days of receiving their last treatment. Twenty patients (2.3% of total; 11.2% of expired patients) received RT within their last week of life. For both sites, the median time until death from completion of therapy was 12.5 days (range 2–30 days).

Conclusions

Radiation in the last month of life is likely to provide minimal palliation or survival benefit. This, coupled with the financial implications, time investment, and physical costs, suggests that physicians and patients should more strongly consider hospice, and minimize duration of palliative RT courses as far as possible. As with chemotherapy, RT utilization at EOL should be considered for collection as an overuse metric.     

Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis

Objective

We performed a meta-analysis of randomized clinical trials to compare the efficacy of brain radiotherapy (RT) combined with temozolomide (TMZ) versus RT alone as first-line treatment for brain metastases (BM).

Methods

Medline, Embase, and Pubmed were used to search for relevant randomized controlled trials (RCTs). Two investigators reviewed the abstracts and independently rated the quality of trials and relevant data. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and adverse events.

Results

Seven studies were selected from the literature search. RT plus TMZ produced significant improvement in ORR with odds ratio (OR) of 2.27 (95% CI, 1.29 to 4.00; P = 0.005) compared with RT alone. OS and PFS were not significantly different between the two arms (OS: HR, 1.00; P = 0.959; PFS: HR, 0.73; P = 0.232). However, the RT plus TMZ arm was associated with significantly more grade 3 to 4 nausea and thrombocytopenia.

Conclusion

Concomitant RT and TMZ, compared to RT alone, significantly increases ORR in patients with BM, but yields increased toxicity and fails to demonstrate a survival advantage.     

Endoscopic Resection Compared with Gastrectomy to Treat Early Gastric Cancer: A Systematic Review and Meta-Analysis

Background

Endoscopic resection and gastrectomy are treatment modalities for early gastric cancer, but their relative benefits and risks are unclear. We conducted a systematic review and meta-analysis to compare endoscopic resection and gastrectomy for treating early gastric cancer.

Methods

We searched PubMed, Embase, and the Cochrane Library until April 2015 for studies comparing endoscopic resection with gastrectomy for treatment of early gastric cancer. Outcome measures were five-year overall survival (OS), length of hospital stay and postoperative morbidity. We calculated pooled hazard ratio (HR), weighted mean difference (WMD) and odds ratio (OR) using random effects models.

Results

Six studies comprising 1,466 patients (618 endoscopic resection and 848 gastrectomy) met inclusion criteria. Five-year OS was similar between endoscopic resection and gastrectomy (HR, 1.06; 95%CI: 0.61 to 1.83). Endoscopic resection was associated with shorter hospital stays (WMD, -6.94; 95%CI: -7.59 to -6.29) and reduced overall postoperative morbidity (OR, 0.36; 95%CI: 0.17 to 0.74).

Conclusions

While five-year OS is similar between endoscopic resection and gastrectomy, endoscopic resection offers a shorter hospital stay and fewer complications than gastrectomy for treating early gastric cancer. Endoscopic resection is a reasonable treatment for early gastric cancer with a negligible risk of lymph node metastasis.     

Perioperative Chemotherapy in Gastroesophageal Cancer. A Retrospective Monocenter Evaluation of 42 Cases

Background

Perioperative chemotherapy increases the overall and progression-free survival of patients suffering from resectable adenocarcinomas of the lower esophagus, gastroesophageal junction and stomach (GEC). Comparing different chemotherapy regimens platin-based protocols with 5-fluorouracil (5-FU)/calcium folinate (CF) or oral fluoropyrimidines were favorable in terms of efficacy and side-effects. However, there is no consensus which regimen is the most efficacious.

Methods

42 consecutive patients with resectable GEC (UICC II and III) were treated with 3 pre- and postoperative chemotherapy cycles each consisting of epirubicin, oxaliplatin and capecitabine (EOX). We analyzed the overall survival, progression-free survival and toxicity retrospectively in comparison to published data.

Results

The median overall survival in our cohort was 29 months and the progression-free survival was 17 months. The most frequent grade 3 and 4 toxicities during preoperative chemotherapy were diarrhea (16.7%), leukocytopenia (9.5%) and nausea (9.5%); overall 38.1% of our patients suffered from grade 3 or 4 toxicity. Surgery was carried out in 83% of our patients, 69% of those achieved R0 resection.

Conclusion

Comparing our data with the results of previously published randomized trials EOX is at least non-inferior with regard to overall survival, progression-free survival and toxicity. In conclusion, EOX is an appropriate perioperative therapy for patients with resectable GEC.