Multimodality treatment with intensity modulated radiation therapy for esophageal cancer

The objective of this study is to determine the feasibility and report the outcome of patients with locally advanced esophageal cancer treated with preoperative or definitive chemoradiotherapy (CRT) using intensity‐modulated radiation therapy (IMRT). Between 2003 and 2007, 30 patients with non‐cervical esophageal cancer received concurrent chemotherapy and IMRT at Stanford University. Eighteen patients were planned for definitive CRT and 12 were planned for preoperative CRT. All patients had computed tomography‐based treatment planning and received IMRT. The median dose delivered was 50.4 Gy. Patients planned for preoperative CRT underwent surgery 4–13 weeks (median 8.3 weeks) following completion of CRT. Median follow‐up of surviving patients from start of RT was 24.2 months (range 8.2–38.3 months). The majority of tumors were adenocarcinomas (67%) and poorly differentiated (57%). Tumor location was 7% upper, 20% mid, 47% lower, and 27% gastroesophageal junction. Actuarial 2‐year local‐regional control (LRC) was 64%. High tumor grade was an adverse prognostic factor for LRC and overall survival (OS) (P= 0.015 and 0.012, respectively). The 2‐year LRC was 83% vs. 51% for patients treated preoperatively vs. definitively (P= 0.32). The 2‐year disease‐free and OS were 38% and 56%, respectively. Twelve patients (40%) required feeding tube placement, and the average weight loss from baseline was 4.8%. Twelve (40%) patients experienced grade 3+ acute complications and one patient died of complications following feeding tube placement. Three patients (10%) required a treatment break. Eight patients (27%) experienced grade 3 late complications. No grade 4 complications were seen. IMRT was effective and well tolerated. Disease recurrence remains a challenge and further investigation with dose escalation to improve LRC and OS is warranted.     

Prospective non‐randomized study of preoperative concurrent platinum plus 5‐fluorouracil‐based chemoradiotherapy with or without paclitaxel in esophageal cancer patients: long‐term follow‐up

Combined modality treatment for esophageal carcinoma seems to improve survival over surgery alone. Different combinations of cytotoxic drugs have been studied to improve antitumor efficacy and limit the toxicity of chemoradiotherapy (CRT) with inconsistent results. We present a prospective study of neoadjuvant CRT with or without paclitaxel in chemotherapy schedule. One hundred seven patients (93 males, 14 females), median age 59 years (range 44–76), with operable esophageal cancer were enrolled. They received the following neoadjuvant therapy: Carboplatin, area under curve (AUC) = 6, intravenously on days 1 and 22, 5‐fluorouracil (5‐FU), 200 mg/m²/day, continuous infusion on days 1 to 42, radiation therapy 45 grays/25fractions/5 weeks beginning on day 1. Forty‐four patients (41%) were furthermore non‐randomly assigned to paclitaxel 200 mg/m²/3 h intravenously on days 1 and 22. Nutritional support from the beginning of the treatment was offered to all patients. Surgery was done within 4–8 weeks after completion of CRT, if feasible. All patients were evaluated for grade 3 plus 4 toxicities: leukopenia (28%), neutropenia (30%), anemia (6%), thrombocytopenia (31%), febrile neutropenia (6%), esophagitis (24%), nausea and vomiting (7%), pneumotoxicity (8%). Seventy‐eight patients (73%) had surgery and 63 of them were completely resected. Twenty‐two patients (20%) achieved pathological complete remission, and additional 20 (19%) had node‐negative and esophageal wall‐positive residual disease. There were 10 surgery‐related deaths, mostly due to pulmonary insufficiency. Twenty‐nine patients were not resected, 15 for early progression, 14 for medical reasons or patient refusal. After a median follow‐up of 52 months (range 27–80), median survival of 18.0 months and 1‐, 2‐, 3‐ and 5‐year survival of 56.7, 37.5, 27.0 and 21% was observed in the whole group of 107 patients. Addition of paclitaxel to carboplatin and continual infusion of FU significantly increased hematologic and non‐hematologic toxicity, but treatment results as overall survival or time to progression did not differ significantly in groups with and without paclitaxel. Patients achieving pathological complete remission or nodes negativity after neoadjuvant therapy had favorable survival prognosis, whereas long‐term prognosis of node positive patients was poor. Distant metastases prevailed as a cause of the treatment failure. Factors significant for survival prognosis in multivariate analysis were postoperative node negativity, performance status, and grade of dysphagia. Addition of paclitaxel to carboplatin and continual FU significantly increased hematologic and non‐hematologic toxicity without influencing efficacy of the treatment. This study confirmed improved prognosis of patients after achieving negativity of nodes. Distant metastases prevailed as cause of the treatment failure. Prospectively, it is important to look for a therapeutic combination with better systemic effect.     

Comparative outcomes for three‐dimensional conformal versus intensity‐modulated radiation therapy for esophageal cancer

Emerging data suggests a benefit for using intensity modulated radiation therapy (IMRT) for the management of esophageal cancer. We retrospectively reviewed patients treated at our institution who received definitive or preoperative chemoradiation with either IMRT or 3D conformal radiation therapy (3DCRT) between October 2000 and January 2012. Kaplan Meier analysis and the Cox proportional hazard model were used to evaluate survival outcomes. We evaluated a total of 232 patients (138 IMRT, 94 3DCRT) who received a median dose of 50.4 Gy (range, 44–64.8) to gross disease. Median follow up for all patients, IMRT patients alone, and 3DCRT patients alone was 18.5 (range, 2.5–124.2), 16.5 (range, 3–59), and 25.9 months (range, 2.5–124.2), respectively. We observed no significant difference based on radiation technique (3DCRT vs. IMRT) with respect to median overall survival (OS) (median 29 vs. 32 months; P = 0.74) or median relapse free survival (median 20 vs. 25 months; P = 0.66). On multivariable analysis (MVA), surgical resection resulted in improved OS (HR 0.444; P < 0.0001). Superior OS was also associated on MVA with stage I/II disease (HR 0.523; P = 0.010) and tumor length ≤5 cm (HR 0.567; P = 0.006). IMRT was also associated on univariate analysis with a significant decrease in acute weight loss (mean 6% + 4.3% vs 9% + 7.4%, P = 0.012) and on MVA with a decrease in objective grade ≥3 toxicity, defined as any hospitalization, feeding tube, or >20% weight loss (OR 0.51; P = 0.050). Our data suggest that while IMRT‐based chemoradiation for esophageal cancer does not impact survival there was significantly less toxicity. In the IMRT group there was significant decrease in weight loss and grade ≥3 toxicity compared to 3DCRT.     

Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer

INTRODUCTION Cervical esophageal cancer occurs rarely and accounts for only 2%-10% of all esophageal carcinomas in the United States[1]. Surgery, an option only for patients with early-stage tumors, generally requires a total laryngopha ryngoesophagectomy…     

Obesity and outcomes in patients treated with chemoradiotherapy for esophageal carcinoma

Body mass index (BMI) is a risk factor for comorbid illnesses and cancer development. It was hypothesized that obesity status affects disease outcomes and treatment‐related toxicities in esophageal cancer patients treated with chemoradiotherapy (CRT). From March 2002 to April 2010, 405 patients with non‐metastatic esophageal carcinoma at MD Anderson Cancer Center treated with either definitive or neoadjuvant CRT were retrospectively analyzed. Patients were categorized as either obese (BMI ≥ 25 kg/m²) or nonobese (BMI < 25 kg/m²). Progression‐free survival and overall survival times were examined using the Kaplan–Meier method and Cox proportional hazards regression analysis. One hundred fifteen (28.4%) patients were classified as nonobese and 290 (71.6%) as obese. Obese patients were more likely than others to have several comorbid diseases (P < 0.001), adenocarcinoma located distally (P < 0.001), and have undergone surgery (P = 0.004). Obesity was not associated with either worse operative morbidity/mortality (P > 0.05) or worse positron emission tomography tumor response (P = 0.46) on univariate analysis, nor with worse pathologic complete response (P = 0.98) on multivariate analysis. There was also no difference in overall survival, locoregional control, or metastasis‐free survival between obese and nonobese patients (P = 0.86). However, higher BMI was associated with reduced risk of chemoradiation‐induced high‐grade esophagitis (P = 0.021), esophageal stricture (P < 0.001), and high‐grade hematologic toxicity (P < 0.001). In esophageal cancer patients treated with CRT, obesity is not predictive of poorer disease outcomes or operative morbidities; instead, data suggest it may be associated with decreased risk of acute chemotherapy‐ and radiotherapy‐related treatment toxicities.     

Toxicity and outcomes after chemoradiation for esophageal cancer in patients age 75 or older

Randomized trials of chemoradiation for esophageal cancer have included very few patients age ≥ 75. In this retrospective study, we describe the outcomes and toxicity of full‐dose chemoradiation in elderly patients with esophageal cancer. Patients, age ≥ 75, treated with full‐dose chemoradiation for esophageal carcinoma from 2002 to 2008 were retrospectively reviewed. Thirty‐four patients were identified with a median age of 79.5 (range 75–89). The median Eastern Cooperative Oncology Group performance status was 1 (range 0–3) and the median Adult Comorbidity Evaluation‐27 score was 1 (range 0–3). Twenty‐eight patients received definitive and six received neoadjuvant chemoradiation. The median radiation dose delivered was 50.4 Gray (range 3.6–68.4 Gray). Platinum‐based chemotherapy was used in 79.4% of patients. Fifty percent of the patients completed all planned radiation therapy (RT) and chemotherapy; 85.3% completed RT. Acute toxicity ≥ grade 4 occurred in 38.2% of patients, and 70.6% of the patients required hospitalization, emergency department visit, and/or RT break. Median follow‐up was 14.5 months among 7 survivors, and median survival was 12.0 months (95% confidence interval [CI]: 9.7 to 24.1 months). The actuarial overall survival at 2 years was 29.7% (95% CI: 16.6 to 52.6%). There were four treatment‐related deaths. The median time to any recurrence was 10.4 months. Nineteen patients had a local and/or distant recurrence. In conclusion, elderly patients experienced substantial morbidity from chemoradiation, and long‐term survival was low. Future efforts to improve treatment tolerability in the elderly are needed.     

Postoperative chemoradiotherapy after surgical resection of gastric adenocarcinoma: can LV5FU2 reduce the toxic effects of the MacDonald regimen?: A report on 23 patients

AIM OF THE STUDY: A North American phase III trial has recently shown that postoperative chemoradiotherapy using the FUFOL Mayo Clinic regimen improves overall survival and relapse-free survival after surgical resection of gastric cancer. However, severe grade 3-4, hematologic and gastrointestinal toxicities were frequent. The aim of this retrospective and multicentric study was to determine the tolerance of a postoperative chemoradiotherapy regimen using LV5FU2 instead of the Mayo Clinic regimen. PATIENTS AND METHODS: Twenty-three patients with resected adenocarcinoma of the stomach or gastroesophageal junction at high risk of recurrence were treated with LV5FU2 chemotherapy and radiotherapy (45 Gy in 25 fractions and 5 weeks) delivered to the tumor bed and regional nodes. Nineteen patients were treated with two to four cycles before radiotherapy, then three cycles during radiotherapy, and finally four cycles after radiotherapy; four patients were only given three cycles during radiotherapy. RESULTS: Of the 23 patients assigned to this protocol, 20 completed treatment (87%). There was only one interruption of treatment because of hematologic or gastrointestinal toxicity. Tolerance of LV5FU2 regimen associated with radiotherapy was excellent: one grade 3 or 4 gastrointestinal toxicity (4.3%), no toxic death, and only one grade 3 neutropenia (4.3%) were reported. CONCLUSION: Radiotherapy combined with LV5FU2 appears to be better tolerated than the Mayo Clinic regimen used in the North American study. These results have to be considered when elaborating future postoperative chemoradiotherapy trials for gastric cancer.     

Adjuvant radiotherapy for gallbladder cancer: a dosimetric comparison of conformal radiotherapy and intensity-modulated radiotherapy

AIM: To assess the efficacy and toxicity of conformal radiotherapy (CRT) and compare with intensity-modulated radiotherapy (IMRT) in the treatment of gallbladder cancer. METHODS: Between November 2003 and January 2010, 20 patients with gallbladder cancer were treated with CRT with or without chemotherapy after surgical resection. Preliminary survival data were collected and examined using both Kaplan-Meier and actuarial analysis. Demographic and treatment parameters were collected. All patients were planned...     

Comparison of preoperative chemotherapy using docetaxel,cisplatin and fluorouracil with cisplatin and fluorouracil in patients with advanced carcinoma of the thoracic esophagus

We retrospectively compared preoperative docetaxel, cisplatin, and fluorouracil (DCF) with cisplatin and fluorouracil (CF) in patients with esophageal cancer. The study included patients with advanced thoracic esophageal carcinoma (excluding T4 tumors) receiving preoperative chemotherapy. In the DCF group, five patients received two courses of treatment every 4 weeks, and 33 patients received three courses every 3 weeks. In the CF group, 38 patients received two courses of treatment every 4 weeks. Patients underwent curative surgery 4–5 weeks after completing chemotherapy. Patient demographic characteristics did not differ between the two study groups. The incidence of a grade 3 or 4 hematologic toxicity was significantly higher in the DCF group (33 patients) than in the CF group (five patients; P < 0.001). Curative resection was accomplished in 79% of patients in the DCF group and 66% in the CF group (P = 0.305). There were no in‐hospital deaths. The incidence of perioperative complications did not differ between the groups. A grade 2 or 3 histological response was attained in a significantly higher proportion of patients in the DCF group (63%) than in the CF group (5%; P < 0.001). Progression‐free survival and overall survival were significantly higher in the DCF group (P = 0.013, hazard ratio 0.473; P = 0.001, hazard ratio 0.344). In conclusion, a grade 3 or 4 hematologic toxicity was common in the DCF group but was managed by supportive therapy. Histological response rate, progression‐free survival, and overall survival were significantly higher in the DCF group compared with the CF group.     

Phase Ⅰ study of postoperative radiotherapy combined with capecitabine for gastric cancer

AIM:To determine the maximum tolerated dose(MTD)and dose-limiting toxicity(DLT)of capecitabine combined with postoperative radiotherapy for gastric cancer.METHODS:We enrolled patients with any T stage and node-positive gastroesophageal or gastric adenocarcinoma after complete resection with negative margins(R0)or microscopic(R1)or macroscopic(R2)resection.Intensity modulated radiotherapy(IMRT)using a fiveto-seven-field,coplanar,sliding window technique was delivered to the tumor bed(T4b),anastomosis site,duodenal stump and regional lymph nodes(LNs)to a total dose of 45 Gy(1.8 Gy/fraction,5 d/wk).Patients with R1 or R2 resection received 10.8 Gy as a boost.Capecitabine was administered twice daily on every radiotherapy treatment day in a dose-escalation schedule (mg/m2)of 625(levelⅠ,n=6),700(levelⅡ,n=6),800(levelⅢ,n=6),900(levelⅣ,n=0)and 1000(levelⅤ,n=0).DLT was defined as grade 4 leukopenia or neutropenia,grade 3-4 thrombocytopenia or anemia and grade 3-4 non-hematological toxicity.RESULTS:Between October 2007 and August 2009,18 patients(12 men,6 women;median age,54 years)were enrolled in the study.The median number of positive LNs was 6,and total number of resected LNs was19.Twelve patients underwent R0 resection(66.7%).Fifteen patients received adjuvant chemotherapy under the leucovorin,fluorouracil and oxaliplatin(FOLFOX4)regimen.Six patients each were enrolled at dose levelsⅠ,ⅡandⅢ.Grade 1-3 leukopenia(16 patients,88.9%),anorexia(15,83.3%)and nausea(15,83.3%)were the most common toxicities.Grade 3 anorexia/nausea and grade 4 vomiting occurred in one level-Ⅰpatient.Grade 3 anorexia and nausea occurred in one level-Ⅱpatient.One level-Ⅲpatient developed grade 4neutropenia,while another developed grade 3 radiation esophagitis.No abnormal liver or renal function examinations were observed.Three patients did not finish chemoradiotherapy because of DLTs and two without DLTs received sequential boosts(total dose,55.8 Gy).CONCLUSION:The MTD of capecitabine was 800 mg/m2twice daily concurrent with IMRT for gastric cancer after surgery.The DLTs were anorexia/nausea,vomiting,neutropenia and radiation esophagitis.     

Resection surgery with neoadjuvant chemoradiotherapy improves outcomes of patients with T4 esophageal carcinoma

The prognosis of patients with T4 esophageal carcinoma is poor, and thus an effective treatment needs to be established. The present study assessed the effect of chemoradiotherapy (CRT), postoperative morbidity and mortality, and survival time in 41 patients with T4 esophageal carcinoma. Of these, 24 received CRT followed by surgery (group A) and the remaining 17 were treated with CRT alone (group B). Postoperative complications in group A were compared with 251 patients (group C) who underwent surgery without CRT during the same period. Postoperative complications were more frequent in group A than group C (29.2% vs 8.4%, P < 0.05). The overall median survival of group A was statistically longer than that of group B (13.8 months and 3.3 months respectively, P < 0.001). Complete histologic response (grade 3) was documented in 4 group A patients (16.7%). The overall median survival of grade 3 patients was statistically longer than the rest of group A (38.9 months vs 8.8 months, P < 0.05). The data confirm that chemoradiotherapy creates tumor regression in some patients and allows resection surgery in T4 esophageal carcinoma. Moreover, surgery with CRT confers a survival advantage in T4 esophageal carcinoma.     

Predictors of response and survival for neoadjuvant treated patients with esophageal adenocarcinoma

SUMMARY. Mainly patients with advanced esophageal adenocarcinoma who respond to neoadjuvant chemotherapy show a significant survival benefit after resection. Therefore, prediction of response before treatment is desirable. The aim of this study was to assess genetic predictors of response and survival for patients with esophageal adenocarcinoma prior to neoadjuvant therapy. Thirty‐two patients with advanced esophageal adenocarcinoma who underwent neoadjuvant therapy with resection of their tumor were analyzed for thymidylate synthase (TS), excision repair cross complementing (ERCC1) and Gluthatione S‐transferase (GSTP‐1) mRNA levels prior to the treatment. These results were analyzed in regards of response and survival. In total, 18 patients responded to this protocol. Seventeen of those did show a gene expression level at or below the respective median of at least one gene. This had a profound impact on survival, demonstrating an increase in survival for patients who have TS, ERCC1, or GSTP‐1 mRNA level at or below the median. These results demonstrate a potential predictive value of a gene expression profile available prior to therapy. These data have to be confirmed by a larger prospective trial.     

Toxicity data for preoperative concurrent chemoradiotherapy with oxaliplatin and continuous infusion 5‐fluorouracil for locally advanced esophageal cancer

The purpose of this retrospective analysis was to characterize the feasibility and tolerability of oxaliplatin/5‐fluorouracil (5‐FU) given concurrently with radiotherapy for patients with locally advanced esophageal cancer. Between July 2005 and March 2009, 15 patients with clinical stage T3/T4 and/or N1/M1a lower esophageal or gastroesophageal junction adenocarcinoma were treated with preoperative chemoradiotherapy using oxaliplatin every 2 weeks and continuous infusion 5‐FU. The main treatment‐related toxicities were oral mucositis and dysphagia. During the first 2 weeks of treatment, 20% of patients presented with grade 1–2 oral mucositis, and one patient developed grade 1 dysphagia. In weeks 3–4, 53% of the patients experienced grade 1–2 mucositis, and 40% experienced grade 1–2 dysphagia. One patient only experienced grade 3 mucositis in week 4. Three patients (20%) had grade 3–4 dysphagia in weeks 3–4 and were continued on intravenous fluids and pain medications. During the last 2 weeks of chemoradiotherapy, 53% of patients reported grade 1–2 oral mucositis, mostly grade 1 and 73% of patients experienced grade 1–2 dysphagia and 26% patients experienced grade 3–4 dysphagia. Other toxicities included fatigue, nausea, neuropathy, and diarrhea. Only one patient experienced > 10% weight loss. The whole group was treated with aggressive supportive care during radiotherapy. Five (33%) patients achieved a pathological complete response. No patients developed locoregional failure. Sixty percent of the patients developed distant metastases and the 2‐year disease‐free survival was 53%. The median survival was 3.2 years with the 2‐year overall survival of 73%. Preoperative oxaliplatin/5‐FU‐based chemoradiotherapy for locally advanced esophageal cancer is feasible, but associated with substantial gastrointestinal toxicity. A careful attention to nutrition and hydration throughout the course of therapy is required.     

Salvage radiation therapy and chemoradiation therapy for postoperative locoregional recurrence of esophageal cancer

The purpose of this retrospective study was to assess the efficacy of salvage radiation therapy (RT) or chemoradiation therapy (CRT) for locoregional recurrence (LR) of esophageal cancer after curative surgery. Forty‐two patients who received salvage RT or CRT for LR of esophageal cancer after curative surgery between November 2000 and May 2012 were reviewed. The intended RT regimen was 60 Gy in 30 fractions combined with concurrent platinum‐based chemotherapy. Median follow‐up periods were 17.9 months for all evaluable patients and 28.2 months for patients still alive (19 patients) at analysis time. The 1‐, 2‐, and 3‐year survival rates were 81.2 ± 6.4%, 51.3 ± 8.6%, and 41.1 ± 8.7%, respectively, with a median survival time of 24.3 ± 4.1 months. Out of 41 evaluable patients, 16 patients (39%) were alive beyond 2 years from salvage therapy. However, univariate analyses for overall survival showed no significant prognostic factor. Grade 3 or higher leukocytopenia was observed in 46% of the patients. Salvage RT or CRT for LR after surgery for esophageal cancer was safe and effective. These therapies may offer long‐term survival to some patients. RT or CRT should be considered for LR.     

Esophageal cancer: definitive chemoradiotherapy for elderly patients

To investigate the efficacy and toxicity of definitive chemoradiotherapy (CRT) for elderly patients with locally advanced esophageal cancer. Twenty‐two patients aged over 75 that performed definitive CRT were retrospectively reviewed. The regimen included concurrent CRT consisting of two cycles of chemotherapy (CTx) of platinum and 5‐fluorouracil, and radiation therapy (RT) of 50–50.4 Gy (actual range: 45.4–71.4 Gy), and additional CTx where possible. Both CTx and RT were reduced in dose and field where necessary. The disease‐free survival rate and the overall survival rate at 3 years were 33.3% ± 11.4% and 25.9% ± 10.8%. Grade 4 leukocytopenia and thrombocytopenia occurred in three (14%) and four (18%) patients. Treatment‐related death was suspected in up to four (18%) patients at the most. Univariate analyses for disease‐free survival showed that neither total radiation dose nor number of total cycles of CTx was significant. The pattern of relapse was predominantly more frequent in the intra‐RT field than outside the RT field. For elderly patients, adverse events are frequent, and decreased organ reserve may cause treatment‐related death. Reduction in CTx dose or RT field, appropriate only for two cycles of CTx, and careful monitoring may help to minimize toxicity. Physicians should not be too afraid of adverse events or be negative about CRT for elderly patients, as long as comorbidities and complications are managed carefully.     

Comparison of salvage chemoradiation versus salvage surgery for recurrent esophageal squamous cell carcinoma after definitive radiochemotherapy or radiotherapy alone

A consensus treatment strategy for esophageal squamous cell carcinoma (ESCC) patients who recur after definitive radiochemotherapy/radiotherapy has not been established. This study compared the outcomes in ESCC patients who underwent salvage surgery, salvage chemoradiation (CRT) or best supportive care (BSC) for local recurrence. Ninety‐five patients with clinical stage I to III ESCC who had completely responded to the initial definitive radiochemotherapy or radiotherapy alone and developed local recurrence were enrolled in this study. Fifty‐one of them received salvage esophagectomy, and R0 resection was performed in 41 patients, 36 underwent salvage CRT, and the remaining eight patients received BSC only. The 5‐year overall survival was 4.6% for the 87 patients receiving salvage surgery or CRT, while all patients in the BSC group died within 12.0 months, the difference was statistically significant (P = 0.018). The 1‐, 3‐, 5‐year survival rates in the salvage surgery and salvage CRT groups were 45.1%, 20.0%, 6.9% and 51.7%, 12.2%, 3.1%, respectively, there was no difference of overall survival between the two groups (P = 0.697). Patients also presented with lymph node relapse had inferior survival compared to those with isolated local tumor recurrence after salvage therapy. In the salvage surgery group, infections occurred in eight patients, and three developed anastomotic leakage. In the salvage CRT group, grade 2–4 esophagitis and radiation pneumonitis was observed in 19 and 3 patients, respectively. Seven patients (19.4%) developed esophagotracheal fistula or esophageal perforation. This study of salvage CRT versus salvage surgery for recurrent ESCC after definitive radiochemotherapy or radiotherapy alone did not demonstrate a statistically significant survival difference, but the frequency of complications including esophagotracheal fistula and esophageal perforation following salvage CRT was high.     

The addition of induction chemotherapy with etoposide, ifosfamide, and cisplatin failed to improve therapeutic outcome of concurrent chemoradiotherapy in patients with locally advanced non-small cell lung cancer -- single institution retrospective analysis

Although chemoradiotherapy (CRT) is a standard treatment for unresectable locally advanced non-small cell lung cancer (NSCLC), the optimal sequencing remains to be determined. We retrospectively compared the treatment results of induction chemotherapy followed by concurrent CRT (induction group, 32 patients) with those of concurrent CRT alone (concurrent group, 41 patients) in unresectable stage IIIA/IIIB NSCLC patients. In induction group, 2 cycles of induction chemotherapy (etoposide/ifosfamide/cisplatin: 24 patients, others: 8 patients) were followed by concurrent CRT (60 Gy/30 fractions, 6 mg/m2 of cisplatin daily), while the same concurrent CRT was administered in concurrent group. Clinicopathologic characteristics including age, weight loss, histologic types, and clinical stage did not show significant differences between two groups except for a higher proportion of patients with ECOG performance status 2 in concurrent group (3% vs. 27%, p=0.015). Overall toxicity was generally acceptable with 1 treatment-related death from tracheoesophageal fistula in induction group. The response rates after concurrent CRT were 41% for induction group and 54% for concurrent group, which showed no significant difference (p=0.560). With median follow-up of 13 (1-92) months, there was a trend toward an advantage for concurrent group in median progression-free survival (6 months vs 8.3 months, p=0.067) and overall survival (12 months vs. 14.5 months, p=0.059). In multivariate analysis, only more than 10% weight loss within 6 months was significantly associated with poor survival (p=0.001). In conclusion, the addition of induction chemotherapy to concurrent CRT did not show any advantage over concurrent CRT alone in locally advanced NSCLC.     

Feasibility of endoscopic mucosal resection as salvage treatment for patients with local failure after definitive chemoradiotherapy for stage IB,II, and III esophageal squamous cell cancer

Local failure after definitive chemoradiotherapy (CRT) for stage IB, II, and III esophageal cancer is one of the causes of poor outcome. Endoscopic mucosal resection (EMR) is an effective treatment for superficial esophageal cancer. However, its feasibility as a salvage treatment for local recurrent or residual tumors after definitive CRT for stage IB, II, and III esophageal cancer remains unclear. Between January 2000 and February 2008, 274 patients with stage IB, II, and III esophageal squamous cell cancer excluding T4 received definitive CRT at the National Cancer Center Hospital, Japan. Of these patients, nine patients with local recurrence after achieving complete response and two patients with residual tumor underwent salvage EMR. The technique of salvage EMR involved a strip biopsy method. We retrospectively reviewed the 11 patients (13 lesions). Characteristics of all 11 patients were as follows: median age of 69 (range: 45–78); male/female: 10/1; baseline clinical stage (Union for International Cancer Control 7th) IB/IIA/IIB/III: 1/3/7/0. The depth of resected tumor was limited to the mucosal layer in seven lesions and submucosal in six lesions. En bloc resection was performed on six lesions (46%). The vertical margin was free of cancer cells in 11 lesions (84.6%). No major complications, such as hemorrhage requiring blood transfusion and perforation, were experienced. At a median follow‐up period of 38.9 months (range: 5.3–94 months) after salvage EMR, no recurrence was detected in six patients (54%). Local recurrence was detected in five patients (27%). Of these patients, two had lung metastasis simultaneously, and one was also detected lung metastasis 2 months after the detection of local recurrence. The 5‐year survival rate after salvage EMR was 41.6%. Salvage EMR is a feasible treatment option for local recurrent or residual lesions after definitive chemotherapy and/or radiotherapy for stage IB, II, and III esophageal squamous cell cancer.     

Long‐term results of definitive radiochemotherapy in locally advanced cancers of the cervical esophagus

The aim of this study was to retrospectively analyze the long‐term effectiveness of combined chemoradiation as the definitive treatment of locally advanced cancers of the cervical esophagus. Patients received high‐dose external beam radiotherapy and concurrent cisplatin‐based chemotherapy. Some patients received intraluminal brachytherapy as a boost. In addition, a majority of the patients received cisplatin‐based induction chemotherapy before definitive chemoradiation. Fifty‐five patients (46 men, 9 women, median age 58 years, range 35–72 years) with cancers of the cervical esophagus (stage II: 20; stage III: 35 patients) were treated with definitive chemoradiation (median dose 60 Gy, range 50–70 Gy). Actuarial overall survival rates at 2, 3, 5, and 10 years were 35%, 29%, 25%, and 10%, respectively. Thirteen long‐term survivors were observed with a follow‐up of more than 5 years. Neither gender nor age, tumor length, tumor grade, or clinically detectable lymph node metastases was significant prognostic factors for survival. Twenty‐four patients (44%) developed local or regional recurrences, 15 (27%) distant metastases, and 8 (15%) patients developed a second malignancy. Acute and late toxicity of this treatment schedule was moderate. Concurrent chemoradiation offers a chance of long‐term survival for locally advanced unresectable carcinomas of the cervical esophagus, with long‐term survival rates above 24% and acceptable toxicity. These results substantiate the use of chemoradiation as a curative treatment option for cervical esophageal cancer.     

Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis: long-term results from a phase 2 trial

Light-chain (AL) amyloidosis remains incurable despite recent therapeutic advances. Given the activity of the lenalidomide-alkylating agent combination in myeloma, we designed this phase 2 trial of lenalidomide, cyclophosphamide, and dexamethasone in AL amyloidosis. Thirty-five patients, including 24 previously untreated, were enrolled. Nearly one-half of the patients had cardiac stage III disease and 28% had ≥ 3 organs involved. The overall hematologic response (≥ partial response [PR]) rate was 60%, including 40% with very-good partial response or better. Using serum-free light chain for assessing response, 77% of patients had a hematologic response. Organ responses were seen in 29% of patients and were limited to those with a hematologic response. The median hematologic progression-free survival was 28.3 months, and the median overall survival was 37.8 months. Hematologic toxicity was the predominant adverse event, followed by fatigue, edema, and gastrointestinal symptoms. A grade 3 or higher toxicity occurred in 26 patients (74%) including ≥ grade 3 hematologic toxicity in 16 patients (46%) and ≥ grade 3 nonhematologic toxicity in 25 patients (71%). Seven patients (20%) died on study, primarily because of advanced disease. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) is an effective combination for treatment of AL amyloidosis and leads to durable hematologic responses as well as organ responses with manageable toxicity. The trial was registered at www.clinicaltrials.gov (NCT00564889).