RTOG 0617 compared standard-dose (SD; 60 Gy) versus high-dose (HD; 74 Gy) radiation with concurrent chemotherapy and determined the efficacy of cetuximab for stage III non-small-cell lung cancer ...(NSCLC).
The study used a 2 × 2 factorial design with radiation dose as 1 factor and cetuximab as the other, with a primary end point of overall survival (OS).
Median follow-up was 5.1 years. There were 3 grade 5 adverse events (AEs) in the SD arm and 9 in the HD arm. Treatment-related grade ≥3 dysphagia and esophagitis occurred in 3.2% and 5.0% of patients in the SD arm
12.1% and 17.4% in the HD arm, respectively (
= .0005 and < .0001). There was no difference in pulmonary toxicity, with grade ≥3 AEs in 20.6% and 19.3%. Median OS was 28.7
20.3 months (
= .0072) in the SD and HD arms, respectively, 5-year OS and progression-free survival (PFS) rates were 32.1% and 23% and 18.3% and 13% (
= .055), respectively. Factors associated with improved OS on multivariable analysis were standard radiation dose, tumor location, institution accrual volume, esophagitis/dysphagia, planning target volume and heart V5. The use of cetuximab conferred no survival benefit at the expense of increased toxicity. The prior signal of benefit in patients with higher H scores was no longer apparent. The progression rate within 1 month of treatment completion in the SD arm was 4.6%. For comparison purposes, the resultant 2-year OS and PFS rates allowing for that dropout rate were 59.6% and 30.7%, respectively, in the SD arms.
A 60-Gy radiation dose with concurrent chemotherapy should remain the standard of care, with the OS rate being among the highest reported in the literature for stage III NSCLC. Cetuximab had no effect on OS. The 2-year OS rates in the control arm are similar to the PACIFIC trial.
To present long-term results of RTOG 0915/NCCTG N0927, a randomized lung stereotactic body radiation therapy trial of 34 Gy in 1 fraction versus 48 Gy in 4 fractions.
This was a phase 2 multicenter ...study of patients with medically inoperable non-small cell lung cancer with biopsy-proven peripheral T1 or T2 N0M0 tumors, with 1-year toxicity rates as the primary endpoint and selected failure and survival outcomes as secondary endpoints. The study opened in September 2009 and closed in March 2011. Final data were analyzed through May 17, 2018.
Eighty-four of 94 patients accrued were eligible for analysis: 39 in arm 1 and 45 in arm 2. Median follow-up time was 4.0 years for all patients and 6.0 years for those alive at analysis. Rates of grade 3 and higher toxicity were 2.6% in arm 1 and 11.1% in arm 2. Median survival times (in years) for 34 Gy and 48 Gy were 4.1 versus 4.6, respectively. Five-year outcomes (95% confidence interval) for 34 Gy and 48 Gy were a primary tumor failure rate of 10.6% (3.3%-23.1%) versus 6.8% (1.7%-16.9%); overall survival of 29.6% (16.2%-44.4%) versus 41.1% (26.6%-55.1%); and progression-free survival of 19.1% (8.5%-33.0%) versus 33.3% (20.2%-47.0%). Distant failure as the sole failure or a component of first failure occurred in 6 patients (37.5%) in the 34 Gy arm and in 7 (41.2%) in the 48 Gy arm.
No excess in late-appearing toxicity was seen in either arm. Primary tumor control rates at 5 years were similar by arm. A median survival time of 4 years for each arm suggests similar efficacy, pending any larger studies appropriately powered to detect survival differences.
In 2004, our institution began using four-dimensional computed tomography (4DCT) simulation and then intensity-modulated radiotherapy (IMRT) (4DCT/IMRT) instead of three-dimensional conformal ...radiotherapy (3DCRT) for the standard treatment of non-small-cell lung cancer (NSCLC). This retrospective study compares disease outcomes and toxicity in patients treated with concomitant chemotherapy and either 4DCT/IMRT or 3DCRT.
A total of 496 NSCLC patients have been treated at M. D. Anderson Cancer Center between 1999 and 2006 with concomitant chemoradiotherapy. Among these, 318 were treated with CT/3DCRT and 91 with 4DCT/IMRT. Both groups received a median dose of 63 Gy. Disease end points were locoregional progression (LRP), distant metastasis (DM), and overall survival (OS). Disease covariates were gross tumor volume (GTV), nodal status, and histology. The toxicity end point was Grade >or=3 radiation pneumonitis; toxicity covariates were GTV, smoking status, and dosimetric factors. Data were analyzed using Cox proportional hazards models.
Mean follow-up times in the 4DCT/IMRT and CT/3DCRT groups were 1.3 (range, 0.1-3.2) and 2.1 (range, 0.1-7.9) years, respectively. The hazard ratios for 4DCT/IMRT were <1 for all disease end points; the difference was significant only for OS. The toxicity rate was significantly lower in the IMRT/4DCT group than in the CT/3DCRT group. V20 was significantly higher in the 3DCRT group and was a significant factor in determining toxicity. Freedom from DM was nearly identical in both groups.
Treatment with 4DCT/IMRT was at least as good as that with 3DCRT in terms of the rates of freedom from LRP and DM. There was a significant reduction in toxicity and a significant improvement in OS.
Abstract Elevations in cancer treatment-induced circulating inflammatory cytokines may be partially responsible for the development of significant symptom burden (e.g., pain, fatigue, distress, ...disturbed sleep) during concurrent chemoradiation therapy (CXRT). Sixty-two patients undergoing CXRT for locally advanced non-small cell lung cancer (NSCLC) reported symptoms weekly for 15 weeks via the M. D. Anderson Symptom Inventory (MDASI). Serum inflammatory cytokines were assessed weekly during therapy via enzyme-linked immunosorbent assay. Dynamic changes in cytokines and associated symptom profiles were estimated using mixed-effect models. MDASI symptom severity increased gradually as CXRT dose accumulated and peaked at week 8. Serum concentrations of interleukin (IL)-6, IL-10, and serum soluble receptor 1 for tumor necrosis factor (sTNF-R1) increased significantly by week 8 (all p < .05). During CXRT, controlled for age, sex, race, body mass index, cancer recurrence, previous treatment status, total radiotherapy dose, and CXRT delivery technique, an increase in sTNF-R1 was significantly related to an increase in the mean score for all 15 MDASI symptoms (estimate, 1.74; SE, 0.69; p < .05) and to a larger radiation dose to normal lung volume (estimate, 1.77; SE, 0.71; p < .01); an increase in serum IL-6 was significantly related to increased mean severity for the five most severe symptoms (pain, fatigue, disturbed sleep, lack of appetite, sore throat) (estimate, 0.32; SE, 0.16; p < .05). These results suggest a role for over-expressed pro-inflammatory cytokines in significant worsening of symptoms in NSCLC patients undergoing CXRT, and warrant further study to identify biological targets for ameliorating treatment-related symptom burden.
Background The current American Joint Committee on Cancer (AJCC) esophageal cancer staging for nodal status is difficult to interpret and is based solely on lymph node location relative to the ...primary tumor’s esophageal location. Recent reports suggest that the number of lymph nodes involved is also an important factor. We reviewed our esophageal experience to propose an improved nodal staging system. Methods In all, 1,027 patients with resected esophageal cancer from 1970 to 2005 were reviewed. Lymph nodes stations were assigned according to AJCC criteria. Overall survival was assessed by Kaplan-Meier analysis. The impact of location, number of involved lymph nodes, and use of preoperative chemotherapy or radiation therapy, or both, was assessed. Results Nonregional nodal involvement (n = 17) was associated with decreased survival compared with regional (n = 441) or celiac nodal (n = 73) involvement (3-year: 0% versus 24% and 23%; p < 0.001). The number of involved lymph nodes was strongly associated with survival (3-year: 0 nodes = 63%, 1 to 3 nodes = 31%, more than 3 nodes = 13%; p < 0.001), and multivariable Cox proportional-hazards analysis suggested that the location and number of involved lymph nodes were independent predictors of survival ( p < 0.001). We propose a modified nodal staging system that designates celiac nodes as regional and includes number of involved nodes: pN0, no nodes (3 years = 63%, n = 496); pN1-regional, 1 to 3 nodes (3 years = 32%, n = 292); pN2-regional, more than 3 nodes (3 years = 14%, n = 222); pN3-nonregional node (3 years = 0%, n = 17 p < 0.0001). This modified nodal staging system better predicts survival than the current AJCC nodal staging system in which survival for pN1 (3 years = 24%) and pM1a (3 years = 23%) do not differ ( p = 0.67). The use of induction before surgical resection did not alter the predictive effect of the new nodal staging system. Conclusions Modification of the AJCC nodal classification system to incorporate the number of involved lymph nodes with regional and nonregional node location simplifies and better predicts long-term survival than does the current AJCC nodal system.
To determine the impact of pathologic response following preoperative chemoradiation (CRT) on the AJCC esophageal cancer staging system.
Increasing numbers of locoregionally advanced esophageal ...cancer patients are treated with preoperative CRT prior to surgical resection.
Five hundred ninety-three pts from 1985 to 2003 with esophageal cancer who underwent surgery with (n = 239) or without CRT (n = 354) were reviewed. Resected esophageal tumors were assessed for pathologic response by determining extent of residual tumor following CRT (P0, 0% residual; P1, 1%-50% residual; P2, >50% residual).
After CRT down-staging, pTNM specific survival was similar, irrespective of treatment group (P = 0.98). The pTNM stage distribution was more favorable in the CRT group (P < 0.001) despite a more advanced initial cTNM stage distribution (P < 0.001). Following CRT, the pathologic response (pP) at the primary tumor as defined by extent of residual tumor predicted overall survival (3 years: P0, 0% residual = 74%; P1, 1%-50% residual = 54%; P2, >50% residual = 24%, P < 0.001) and stage specific survival with greater accuracy than pTNM stage alone.
Our analyses demonstrate that following CRT, pTNM continues to predict survival. The extent of pathologic response following CRT is an independent risk factor for survival (pP) and should be incorporated in the pTNM esophageal cancer staging system to better predict patient outcome in esophageal cancer.
Salvage esophagectomy for recurrent tumors after definitive chemotherapy and radiotherapy Swisher, Stephen G.; Wynn, Paula; Putnam, Joe B. ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
January 2002, 20020101, 2002-Jan, 2002-01-00, Letnik:
123, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Objectives: Some patients and oncologists choose to treat localized esophageal cancer with definitive chemotherapy and radiation therapy rather than surgery. A subset of these patients have local ...relapse without distant metastases and therefore have no other curative intent treatment option but salvage esophagectomy. Methods: We reviewed our experience with salvage esophagectomy from 1987 to 2000 at M.D. Anderson Cancer Center (n = 13, salvage after chemotherapy and radiotherapy group) and compared the data with those of patients receiving esophagectomy in a planned fashion 4 to 6 weeks after preoperative chemotherapy and radiation therapy (n = 99, preoperative chemotherapy and radiotherapy group). Results: Increases in morbidity were seen after resection in the salvage after chemotherapy and radiotherapy group relative to the preoperative chemotherapy and radiotherapy group: mechanical ventilation (9.0 days vs 3.3 days, P =.08), intensive care unit stay (11.2 days vs 5.1 days, P =.07), hospital stay (29.4 days vs 18.4 days, P =.03), and anastomotic leak rates (5/13 39% vs 7/99 7%, P =.005). Operative mortality (within 30 days) also tended to be increased statistically nonsignificantly (2/13 15% vs 6/99 6%, P =.2). Salvage esophagectomy resulted in long-term survival (25% 5-year survival) in a subset of patients. Improved survival after salvage esophagectomy was associated with early pathologic stage (T1 N0, T2 N0), prolonged time to relapse, and R0 surgical resection. Conclusion: Patients who undergo salvage esophagectomy for relapse of tumor after definitive chemoradiation therapy have increased morbidity, mortality, and hospital use relative to patients undergoing planned esophagectomy after preoperative chemoradiation. Nevertheless, long-term survival can be achieved in this group, and such treatment should be considered for carefully selected patients at an experienced center.
The objective of the study was to determine the utility of integrated computed tomography / positron emission tomography (CT-PET) imaging for detecting interval distant metastases and assessing ...therapeutic response in patients with locally advanced, potentially resectable esophageal carcinoma after neoadjuvant therapy.
A retrospective study was performed of 88 patients with potentially resectable esophageal carcinoma who received neoadjuvant therapy before planned surgical resection. CT-PET before and after completion of neoadjuvant was used for evaluating therapeutic response; response criteria were based on qualitative and semiquantitative analyses.
Neoadjuvant therapy comprised chemoradiotherapy in 85 patients, with prior induction chemotherapy in 39 patients. Fifty-five patients proceeded to esophagectomy. Repeat CT-PET was performed after induction chemotherapy (n = 23) and after completing chemoradiotherapy (n = 85). CT-PET identified the interval appearance of metastatic disease in 7 (8%) patients. For assessment of locoregional therapeutic response, CT-PET was unable to predict pathological response to neoadjuvant therapy in the primary tumor or locoregional lymph nodes. CT-PET had sensitivity, specificity, and positive and negative predictive values of 57%, 46%, 39%, and 64%, respectively, for detection of residual macroscopic malignancy within the primary tumor; and sensitivity, specificity, and positive and negative predictive values of 0%, 90%, 0%, and 69% for detection of residual malignancy within resected lymph nodes.
CT-PET performed after neoadjuvant therapy in patients with potentially resectable esophageal carcinoma is important for detecting interval metastases that preclude surgical resection, but is of limited utility for assessing locoregional therapeutic response.
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