Early metabolic response to chemoradiotherapy by interim FDG PET/CT is associated with better overall survival and histological response in esophageal cancers
Nassim HammoudiChristophe HennequinLaëtitia VercellinoAdrien CostantiniAraceli ValverdePierre CattanL. Quéro
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Chemoradiotherapy
Standardized uptake value
Complete response
Chemoradiotherapy is a very important factor and one of the 2 pillars of esophageal cancer treatment. Although esophagectomy is the standard treatment for clinical stage Ⅰ(T1N0M0)esophageal cancer, chemoradiotherapy is reported to be effective. Currently, a phaseⅢ clinical trial is underway to compare patients who undergo esophagectomy and those who receive radical chemoradiotherapy. Esophagectomy after neoadjuvant chemotherapy is the standard treatment for clinical stageⅡ/Ⅲ(except for T4) esophageal cancer, whereas chemoradiotherapy is regarded as the standard treatment for patients who wish to preserve their esophagus, those who refuse surgery, and those with inoperable disease. Chemoradiotherapy, rather than surgical treatment, is usually selected for clinical stageⅣ (T4/M1LYM) esophageal cancer. While curability increases with chemoradiotherapy, late adverse events such as cardiopulmonary toxicity and safety problems with salvage treatment of cases with residual tumor or recurrent cancer have been observed. New irradiation techniques using radiation technology are being developed, such as intensity-modulated radiation therapy (IMRT). These innovations are expected to improve treatment results by avoiding irradiation of at-risk organs, without reducing the target radiation volume. New treatments, including salvage protocols, introduction of new radiotherapy equipment such as IMRT, and new drugs, are being developed, and further advances are anticipated.
Chemoradiotherapy
Esophagectomy
Radical surgery
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Chemoradiotherapy
Neoadjuvant Therapy
Complete response
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Radical surgery with extended lymph node dissection has been the main method used for treating patients with resectable esophageal cancer in Japan. Based on data from two phase III studies that compared surgery with or without pre- or postoperative chemotherapy, preoperative chemotherapy followed by surgery emerged as standard treatment for patients with stage II or III disease. Definitive chemoradiotherapy may be an alternative to surgery for those with unresectable as well as resectable esophageal cancer. Recent clinical trials in Japan showed that the survival after definitive chemoradiotherapy was comparable to survival following surgery in stage I disease, with a 5-year survival rate of 75%. However, the 5-year survival rate was worse for chemoradiotherapy (37%) and preoperative chemotherapy followed by radical surgery (60%) for stage II or III disease. In addition, salvage treatment following chemoradiotherapy appeared to be important for patients who did not achieve a complete response or who experienced recurrence. To improve the prognosis for esophageal cancer, a multimodality approach that includes more intensive induction chemotherapy prior to surgery, or possibly chemoradiotherapy containing molecular targeting agents, is preferred. Additional studies are necessary to further elucidate this multimodality approach. Current treatment strategies for esophageal cancer and research initiatives in Japan are reviewed.
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Radical surgery
Induction chemotherapy
Esophagectomy
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The prognosis of patients with locally advanced esophageal cancer treated by surgery alone is poor. The neoadjuvant chemoradiotherapy is considered to improve the long-term survival of patients with locally advanced esophageal cancer. The combination of neoadjuvant chemoradiotherapy and surgery has been recommended to be the standard treatment for the locally advanced esophageal cancer in China even in Europe and America countries. However, available evidence suggests that only those who had histopathologic response seemed to benefit the most from neoadjuvant chemotherapy while non-responders even had rather worse outcome compared to patients with surgery alone. Therefore, predictive markers of response to neoadjuvant chemoradiotherapy in locally advanced esophageal cancer are highly significant and needed. These markers would allow a tailored treatment to guide non-responders to alternative preoperative therapies and ultimately avoid ineffective, costly and seriously cytotoxic treatments. Results of most studies on biomarkers for predicting response to neoadjuvant chemoradiotherapy in esophageal cancer are promising. The potential utilization of biomarkers in clinical practice is urgently expected and needed, which plays an important role in guiding and improving the individualization of multimodality therapy in locally advanced esophageal cancer.
Chemoradiotherapy
Neoadjuvant Therapy
Esophagectomy
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We report a case of advanced esophageal cancer, which was treated by chemoradiotherapy combined with surgical treatment. Moreover, 14 advanced esophageal cancer patients treated by chemoradiotherapy are discussed. The chemoradiotherapy showed beneficial control of the tumor; however, it sometimes leads to esophageal stenosis and ulcer. We conclude that additional salvage surgery is needed for such complications.
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Salvage Surgery
Salvage therapy
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Esophageal cancer is one of the most high incidence of malignant tumors in China.However, the evaluation of chemoradiotherapy curative effect for esophageal cancer is lack of accurate and uniform criteria. In recent years, the imaging evaluation methods for chemoradiotherapy response in esophageal cancer have made some progress. The methods mainly include X-ray barium examination, endoscopic ultrasonography (EUS), computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), and so on. Imaging examination has the advantages of safety, non-invasion and repeatability, and so on, which is a progressing tool for curative effect evaluation. Current status of the application of medical imaging which is used to evaluate esophageal cancer chemoradiotherapy curative effect were reviewed in this paper.
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Esophageal neoplasms; Radiotherapy, computer-assisted; Drug therapy, combination; Medical imaging
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Currently, resectable esophageal cancer is commonly initially treated with surgery in China, but the optimal postoperative treatment remains unclear. Postoperative concurrent chemoradiotherapy can improve local control and reduce distant metastasis and may become the preferred treatment for patients after surgery for esophageal cancer. By summarizing the studies on concurrent chemoradiotherapy after surgery for esophageal cancer, this review points out that postoperative concurrent chemoradiotherapy can improve the overall survival of patients with positive lymph nodes and has tolerable adverse effects, but the populations who can benefit from this treatment, the optimal radiotherapy dosage, target volume, and chemotherapy regimen of postoperative concurrent chemoradiotherapy await further investigation.
Key words:
Esophageal neoplasms/radiochemotherapy; Radiochemotherapy, postoperation; Radiochemotherapy, concurrent
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Esophagectomy
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Esophageal cancer is one of the most common gastrointestinal cancers, and chemoradiotherapy is an important part of the multidisciplinary treatment for this disease. In recent years, 18Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT) is widely used in esophageal cancer for delineation of gross tumor volume, local boost irradiation in the late stage of radiotherapy, and assessment of the pathologic remission rate after neoadjuvant chemoradiotherapy, response to definitive chemoradiotherapy, and prognosis. In this article, we review the application of FDG PET-CT in the chemoradiotherapy for esophageal cancer.
Key words:
Tomography, positron, emission; Fluorine-deoxyglucose; Esophageal neoplasms/chemoradiotherapy
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We assessed the development of lymphopenia during concurrent chemoradiotherapy (CRT) using X-ray versus proton beams and the impact on survival in patients with esophageal cancer. Among patients with esophageal cancer who were administered concurrent CRT with a curative intent at our institute from 2014 to 2018, 69 (15 receiving X-ray radiotherapy (XRT) and 54 receiving proton beam therapy [PBT]) who underwent weekly blood testing during treatment were enrolled. The absolute lymphocyte counts (ALC) at 1, 5 and 6 weeks were significantly higher in the patients who received PBT than in those who received XRT (p = 0.002, p = 0.006 and p = 0.009, respectively), and a similar trend in the neutrophil-to-lymphocyte ratio (NLR) was observed (p = 0.003 at 5 weeks). The 2-year overall survival (OS) and progression-free survival (PFS) rates tended to be higher in the patients who maintained an ALC ≥200 compared with those who did not (p = 0.083 and p = 0.053, respectively), and similar trends were observed in the NLR (p = 0.061 and p = 0.038, respectively). Dose-volume analysis revealed significant correlations between volumes of the thoracic bones irradiated by 5-50 Gy and minimum ALCs and maximum NLR. These findings suggested that PBT prevented the development of lymphopenia during CRT by reducing the irradiated volume of the thoracic bone, and the maintained lymphocyte count is possibly one of the early predictors for survival in patients with esophageal cancer.
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A male in his 40s was diagnosed with type-3 advanced esophageal cancer in the upper thoracic and cervical esophagus, which invaded to the trachea. We administered a low-dose FP combination therapy (5-FU and CDDP) along with 40 Gy radiotherapy. This chemoradiotherapy reduced the esophageal tumor significantly, and then we performed subtotal esophagectomy. Histological examination of the resected specimens revealed no residual cancer cells in the primary lesion or regional lymph nodes. No recurrence had occurred for about three years and seven months after the operation. However, CT revealed that the patient had the signs of recurrence (bone and lung), and finally he died four years and eight months after the operation. Preoperative chemoradiotherapy is potentially effective for advanced esophageal cancer invaded to adjacent organs. Although chemoradiotherapy yielded a complete response in our case( an advanced esophageal cancer patient), a patient follow-up is necessary because a recurrence may occur along the way.
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