Definitive Chemoradiation In Patients Research Articles

Splenic radiation during pancreatic cancer radiotherapy: Are we throwing the baby out with the bath water?

354 Background: Lymphopenia is commonly seen following chemoradiation and is associated with a poor prognosis. We conducted this study to determine if the severity of lymphopenia is dependent on the radiation dose and the fractional volume of spleen irradiated unintentionally during definitive chemoradiation in patients with locally advanced pancreatic cancer (LAPC). Methods: 177 patients with LAPC were treated with induction chemotherapy (FOLFIRINOX or gemcitabine- based regimens) followed by chemoradiation (CRT; median 50.4 Gy with concurrent capecitabine) from 1/2006 to 12/2012. Absolute lymphocyte count (ALC) was recorded at baseline, prior to CRT and 2-10 weeks after the end of CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and the percentage of splenic volume receiving at least 5 Gy (V5), 10 Gy (V10), 15 Gy (V15) and 20 Gy (V20) dose. Overall survival (OS) was analyzed using Cox model and multivariate logistic regression was used to assess the development of post CRT severe lymphopenia (ALC < 0.5 K/UL) using baseline and treatment factors. Results: Median post-CRT ALC (0.68 K/UL, range 0.13 to 2.72) was significantly lower than both baseline (1.42 K/UL, range 0.34- 3.97; p < 0.0001) and pre-CRT ALC (1.32 K/UL, range 0.36- 4.82; p < 0.0001). Post-CRT ALC < 0.5 K/UL was associated with inferior OS on univariate (16.8 vs. 21.2 months, p = 0.004) and multivariate analysis (HR = 1.9, p = 0.002).The MSD was 8.8 Gy and log MSD showed a significant negative correlation (r = -0.18, p = 0.02) with post-CRT ALC. Median V5, V10, V15 and V20 were 34%, 21%, 13% and 8% respectively. Median V10 (32.6 vs. 16%, p = 0.04), V15 (23.2 vs. 9.5%, p = 0.03) and V20 (15.4 vs. 4.6%, p = 0.02) were significantly higher in patients with severe lymphopenia. On multivariate logistic regression analysis, baseline lymphopenia (ALC < 1 K/UL; p = 0.003, OR = 4.6) and MSD (p = 0.03, OR = 7.3) were independent predictors for the development of severe post-CRT lymphopenia. Conclusions: LAPC patients receiving high MSD during CRT are at increased risk of developing severe lymphopenia, which is an independent predictor of poor OS. Routine assessment of splenic DVHs prior to acceptance of treatment plans may minimize this risk.

Predictors of radiation field failure after definitive chemoradiation in patients with locally advanced cervical cancer.

e16518 Background: Concurrent chemoradiotherapy became the standard treatment for locally advanced cervical cancer. However, there is lack of study exploring the predictive factors for the locoregi...

Importance of surveillance and success of salvage strategies after definitive chemoradiation in patients with esophageal cancer.

Patients with esophageal carcinoma (EC) who are treated with definitive chemoradiotherapy (bimodality therapy [BMT]) experience frequent relapses. In a large cohort, we assessed the timing, frequency, and types of relapses during an aggressive surveillance program and the value of the salvage strategies. Patients with EC (N = 276) who received BMT were analyzed. Patients who had surgery within 6 months of chemoradiotherapy were excluded to reduce bias. We focused on local relapse (LR) and distant metastases (DM) and the salvage treatment of patients with LR only. Standard statistical methods were applied. The median follow-up time was 54.3 months (95% CI, 48.4 to 62.4). First relapses included LR only in 23.2% (n = 64), DM with or without LR in 43.5% (n = 120), and no relapses in 33.3% (n = 92) of patients. Final relapses included no relapses in 33.3%, LR only in 14.5%, DM only in 15.9%, and DM plus LR in 36.2% of patients. Ninety-one percent of LRs occurred within 2 years and 98% occurred within 3 years of BMT. Twenty-three (36%) of 64 patients with LR only underwent salvage surgery, and their median overall survival was 58.6 months (95% CI, 28.8 to not reached) compared with those patients with LR only who were unable to undergo surgery (9.5 months; 95% CI, 7.8 to 13.3). Unlike in patients undergoing trimodality therapy, for whom surveillance/salvage treatment plays a lesser role,(1) in the BMT population, approximately 8% of all patients (or 36% of patients with LR only) with LRs occurring more than 6 months after chemoradiotherapy can undergo salvage treatment, and their survival is excellent. Our data support vigilant surveillance, at least in the first 24 months after chemotherapy, in these patients.

Locoregional tumor failure after definitive radiation for patients with stage III non-small cell lung cancer.

BackgroundLocoregional tumor failure (LRF) after definitive chemoradiation for patients with stage III NSCLC remains unacceptably high. This analysis sought to further define where LRF occurs relative to radiation dose received and pre-treatment PET scan-defined maximum standard uptake value (SUVmax).MethodsThis was a retrospective study analyzing patients with stage III NSCLC treated with definitive radiation between 2006 and 2011. LRF was defined as failure within the ipsilateral lung, hilum or mediastinum. The CT simulation scan with the radiation dose distribution was registered to the CT or PET/CT documenting LRF. The region of LRF was contoured, and the dose to 95% of the volume (D95) of LRF was extracted. The pre-treatment SUVmax was also extracted for the anatomic region of LRF.ResultsSixty-one patients were identified. Median follow-up time was 19.1 months (range 2.37-76.33). Seventy four percent of patients were treated with 3-D conformal technique (3DCRT), 15% were treated with Intensity Modulated Radiotherapy (IMRT), and 11% were treated with a combination of 3DCRT and IMRT. Median prescribed radiation dose for all patients was 66 Gy (39.6-74). Concurrent chemotherapy was delivered in 90% of patients. Twenty-two patients (36%) developed a LRF, with a total of 39 anatomic regions of LRF identified. Median time to LRF was 11.4 months (3.5-44.6). Failures were distributed as follows: 36% were in-field failures, 27% were out-of-field failures, 18% were in-field and out-of-field failures, and 18% were in-field and marginal (recurrences within the field edge) failures. There were no isolated marginal failures. Of the patients that developed a LRF, 73% developed a LRF with an in-field component. Sixty-two percent of LRFs were nodal. The median pre-treatment SUVmax for the anatomic region of LRF for patients with an in-field failure was 13. The median D95 of in-field LRF was 63 Gy.ConclusionsLRF after definitive chemoradiation are comprised primarily of in-field failures, though out-of field failures are not insignificant. Marginal failures are rare, indicating field margins are appropriate. Although radiation dose escalation to standard radiation fields has not yielded success, using PET parameters to define high-risk regions remains worthy of further investigation.

Definitive chemoradiation for patients with inoperable and/or unresectable esophageal cancer: locoregional recurrence pattern.

A locoregional recurrence after definitive chemoradiation (dCRT) for patients with inoperable or unresectable esophageal cancer occurs in about 50% of the patients and is a major cause of failure with a poor prognosis. The aim of this study was to determine the pattern of locoregional recurrence and its prognostic factors after dCRT in order to search for improvements in radiation treatment. We retrospectively reviewed 184 patients treated with external beam radiotherapy (50.4 Gray/28 fractions), combined with weekly concurrent paclitaxel and carboplatin. Locoregional recurrences were defined by clinical signs of recurrent or progressive disease, combined with progression on computed tomography/positron emission tomography-computed tomography scan, or suspicious endoscopic findings and/or histological proof of recurrence. The site of locoregional recurrence was analyzed with respect to the borders of the radiation fields. After a mean follow up of 22.8 months, 76 patients (41%) had evidence of locoregional recurrence. The 3-years locoregional recurrence-free rate was 45%. The majority of locoregional recurrences occurred within 12 months, nearly all within 24 months. The majority of these patients failed at the site of the primary tumor (86%). Infield locoregional recurrences at the site of the lymph nodes only occurred in 1% compared with 57% at the site of the primary tumor only. Outfield locoregional lymph node recurrences occurred in 22%, without infield recurrence occurred in only 4% of all patients. The 1-, 3-, and 5-year overall survival was 65%, 28%, and 21%, respectively. The current analysis demonstrates that a locoregional recurrence after dCRT occurs in 41% of the patients, the majority at the site of the primary tumor. These data suggest a benefit of dose intensification of the primary tumor, but not at the site of the lymph nodes. Higher radiation doses should be assessed with prospective trials.

Acute toxicity of definitive chemoradiation in patients with inoperable or irresectable esophageal carcinoma

BackgroundDefinitive chemoradiation (dCRT) is considered curative intent treatment for patients with inoperable or irresectable esophageal cancer. Acute toxicity data focussing on dCRT are lacking.MethodsA retrospective analysis of patients treated with dCRT consisting of 6 cycles of paclitaxel 50 mg/m2 and carboplatin AUC2 concomitant with radiotherapy (50.4 Gy\\1.8Gy) from 2006 through 2011 at a single tertiary center was performed. Toxicity, hospital admissions and survival were analysed.Results127 patients were treated with definitive chemoradiation. 33 patients were medically inoperable, 94 patients were irresectable, Despite of a significantly smaller tumor length in inoperable patients grade ≥3 toxicity was significantly recorded more often in the inoperable patients (44%) than in irresectable patients (20%) (p < 0.05) Hospital admission occurred more often in the inoperable patients (39%) than in the irresectable patients (22%) (p < 0.05) Median number of cycles of chemotherapy was five for inoperable patients (p = 0.01), while six cycles could be administered to patients with irresectable disease. Recurrence and survival were not significantly different. The odds ratio for developing toxicity ≥ grade 3 was 2.6 (95% CI 1.0-6.4 p < 0.05) for being an inoperable patient and 1.2 (95% CI 1.0-1.4 p = 0.02) per 10 extra micromol/l creatinine.ConclusionsOur data show that acute toxicity of definitive chemoradiation is worse in patients with medically inoperable esophageal carcinoma compared to patients with irresectable esophageal cancer and mainly occurs in the 5th cycle of treatment. Improvement of supportive care should be undertaken in this more fragile group.

Expression profile of apoptosis-related genes potentially explains early recurrence after definitive chemoradiation in esophageal squamous cell carcinoma

Definitive chemoradiation is a curative treatment option for patients with locoregional esophageal squamous cell carcinoma (ESCC) who are not suitable for surgical resection, but many tend to develop local recurrence. The purpose of the study was to investigate factors affecting local recurrence of the tumor. Seventy-two patients with stage II-III thoracic ESCC who received definitive concurrent chemoradiation (CRT) and completely responded to the treatment were enrolled into this study. The case patients were 49 patients who recurred locally within 24months after definitive CRT and 23 patients who did not have a local recurrence within 24months were considered as controls. We investigated whether dysregulation of apoptosis-related genes was associated with early tumor recurrence. Quantitative real-time polymerase chain reaction showed upregulation of BCLAF1 and downregulation of BAG4, CARD6, IGF1R, and TNF in the tissues of case patients, as compared with controls. Among the patients with recurrent ESCC, those with tumors which exhibited more than twofold upregulated BCLAF1 and more than twofold downregulated BAG4 and TNF had a decreased time interval to local recurrence. Three gene pairs of the downregulated genes showed a significant correlation with local recurrence: BAG4 and CARD6, BAG4 and TNF, CARD6, and TNF. The patients with T3-4 disease and those with tumor >3cm in length had a trend toward early local recurrence, though the associations were not reached statistical significance. Upregulation of BCLAF1 and downregulation of BAG4 and TNF was independently associated with early local recurrence in multivariate analysis (P < 0.05). This study supports the involvement of apoptosis-related genes in early tumor recurrence after definitive chemoradiation in patients with stage II-III thoracic ESCC.

Multidisciplinary Therapy of Stage IIIA Non—Small-Cell Lung Cancer: Long-term Outcome of Chemoradiation with or without Surgery

Stage IIIA non-small-cell lung cancer (NSCLC) is highly heterogeneous due to differences in the size of the primary tumor and the extent and location of nodal disease. Although the addition of surgery to chemoradiation did not improve overall survival (OS) for stage IIIA patients in a randomized intergroup trial (INT 0139), subset analyses of the trial suggest that a trimodality approach incorporating lobectomy may be superior to bimodality therapy with chemoradiation alone. We analyzed the outcomes of patients with stage IIIA NSCLC (T3N1, T1-3N2) treated at our center between January 2000 and December 2008. We compared OS for those undergoing definitive chemoradiation to those undergoing chemoradiation followed by either lobectomy or pneumonectomy. Demographic variables were balanced by propensity score analysis method. In our analysis of 249 patients, the median age was 65 years, 43% were men, and 96.5% had N2 disease. Chemoradiation followed by lobectomy yielded superior OS compared with chemoradiation (median OS 39 months vs 22 months, P = .038 after propensity score adjustment). There was no significant survival benefit for pneumonectomy over chemoradiation (median survival 28 months vs 22 months, P = .534). Our data corroborate the findings of the INT 0139 trial. We propose that a formal randomized trial be performed comparing chemoradiation followed by lobectomy vs definitive chemoradiation in patients with stage IIIA disease whose tumors are resectable by lobectomy. Our data do not support the incorporation of pneumonectomy in the management of stage IIIA patients with N2 disease.

Up-Front Neck Dissection Followed by Definitive Chemoradiation in Patients with Regionally Advanced Head and Neck Cancer

Up-Front Neck Dissection Followed by Definitive Chemoradiation in Patients with Regionally Advanced Head and Neck Cancer

Oesophagectomy after Definitive Chemoradiation in Patients with Locally Advanced Oesophageal Cancer

Aims The clinical benefit of salvage oesophagectomy in patients who recur after radical chemoradiotherapy (CRT) is not clearly defined. This study retrospectively evaluated the outcome in patients who underwent salvage oesophagectomy having failed primary CRT. Materials and methods Between March 1999 and October 2005, 181 patients with oesophageal cancer were treated at the Royal Marsden Hospital with definitive CRT. Ten patients underwent salvage oesophagectomy. All of them had locally advanced cancer of the oesophagus at presentation (adenocarcinoma in three patients and squamous cell carcinoma in seven patients) and received combined CRT, consisting of 12 weeks of cisplatin and 5-fluorouracil-based chemotherapy followed by CRT. Radiotherapy was delivered with a computed tomography-planned technique to a dose of 54Gy with daily 5-fluorouracil. Results An Ivor–Lewis procedure was carried out in all cases. The median time between the end of CRT and surgery was 5 months (range 1–67). Curative resection was achieved in three patients, seven had microscopic positive circumferential margins. One patient died postoperatively and complications occurred in four cases: anastomotic leak in two patients, pneumonia in one patient, empyema and sepsis in one patient. The median critical care unit stay was 7 days (range 4–26) and hospitalisation was 21 days (range 15–84). With a median follow-up period of 45.5 months (range 5–89) the 1-, 2- and 3-year survival calculated from the completion of CRT was 70, 50 and 30%, respectively. Median survival was 21.5 months (range 8–90). Conclusions Salvage oesophagectomy may prolong survival in carefully selected patients with local relapse. Patients fit for surgery at presentation benefit from a more intensive follow-up protocol to detect early recurrence.

Dose escalation study of docetaxel and nedaplatin in patients with relapsed or refractory squamous cell carcinoma of the esophagus pretreated using cisplatin, 5-fluorouracil, and radiation

Definitive chemoradiation with cisplatin (CDDP) and 5-fluorouracil (5FU) has been playing an important role in the treatment of esophageal cancer, but some patients are not curable or have recurrent lesions. However, few chemotherapeutic regimens are available for such patients. Docetaxel and nedaplatin are active for esophageal cancer. We conducted a dose-escalation study of docetaxel and nedaplatin as second line-chemotherapy after definitive chemoradiation in patients with relapsed or refractory squamous cell carcinoma of the esophagus after chemoradiation. Nedaplatin was administered on day 1 and docetaxel was administered on days 1 and 15, every 4 weeks. Dose escalation was based on the dose-limiting toxicity (DLT) observed during the first cycle. Twelve patients were enrolled. At a docetaxel dose of 30 mg/m(2) and a nedaplatin dose of 80 mg/m(2), one grade 4 neutropenia occurred and caused one treatment break longer than 2 weeks, but there were few DLTs. At doses of 35 and 80 mg/m(2), respectively, two grade 4 neutropenias and one grade 2 thrombopenia occurred and caused three treatment breaks longer than 2 weeks. Therefore, the maximum tolerated dose was established at this dose level. Two grade 3 anorexias and one grade 3 nausea occurred, but other non-hematological toxicities were generally mild. Responses were seen in one-fourth of the 12 patients, including one complete remission. The recommended doses of docetaxel and nedaplatin were 30 and 80 mg/m(2), respectively. This combination could be a potential second-line treatment for this target population.