Ryuta Sasamoto

Retrospective Review of Surgery and Definitive Chemoradiotherapy in Patients with Squamous Cell Carcinoma of the Thoracic Esophagus Aged 75 Years or Older

OBJECTIVE The aim of this study was to review the treatment outcomes of surgery and definitive chemoradiotherapy (CRT) in elderly patients with squamous cell carcinoma of the thoracic esophagus. METHODS A total of 64 patients aged 75 or older were retrospectively reviewed; 40 were treated with surgery and 24 with CRT. The CRT group included eight patients with unresectable disease and four patients medically unfit for surgery. Surgery included esophagectomy with lymphadenectomy and CRT consisted of 60-70 Gy of radiation concurrent with 5-fluorouracil alone or combined with cisplatin. Short- and long-term outcomes and survival of each modality were assessed. RESULTS In the surgery group, 33 patients (82.5%) had co-morbid conditions. Complete resection rate was 90.0%. An overall post-operative complication rate was 65.0% and in-hospital mortality was seen in three patients (7.5%). In the CRT group, complete response rate was 41.7%. Leukopenia was most common Grade 3 hematological toxicity. Treatment-related deaths caused by acute toxicities occurred in three patients (12.5%), whereas those caused by late toxicities in four (16.7%). For cStage I disease in the surgery group, the overall 1-, 3- and 5-year survival rate were 90.9%, 63.6% and 54.5%, respectively, with a median survival time of 78.7 months. For cStages II-IV, the median survival time of the surgery and the CRT group was 18.7 and 12.8 months, respectively. CONCLUSIONS The short- and long-term outcomes of surgery for the elderly seemed acceptable; however, definitive CRT may be a promising treatment modality. Further investigation may alter the sphere of influence in the field of esophageal cancer treatment in the elderly.

Initial implementation of the conversion from the energy-subtracted CT number to electron density in tissue inhomogeneity corrections: An anthropomorphic phantom study of radiotherapy treatment planning

PURPOSE To achieve accurate tissue inhomogeneity corrections in radiotherapy treatment planning, the authors had previously proposed a novel conversion of the energy-subtracted computed tomography (CT) number to an electron density (ΔHU-ρ(e) conversion), which provides a single linear relationship between ΔHU and ρ(e) over a wide range of ρ(e). The purpose of this study is to present an initial implementation of the ΔHU-ρ(e) conversion method for a treatment planning system (TPS). In this paper, two example radiotherapy plans are used to evaluate the reliability of dose calculations in the ΔHU-ρ(e) conversion method. METHODS CT images were acquired using a clinical dual-source CT (DSCT) scanner operated in the dual-energy mode with two tube potential pairs and an additional tin (Sn) filter for the high-kV tube (80-140 kV/Sn and 100-140 kV/Sn). Single-energy CT using the same DSCT scanner was also performed at 120 kV to compare the ΔHU-ρ(e) conversion method with a conventional conversion from a CT number to ρ(e) (Hounsfield units, HU-ρ(e) conversion). Lookup tables for ρ(e) calibration were obtained from the CT image acquisitions for tissue substitutes in an electron density phantom (EDP). To investigate the beam-hardening effect on dosimetric uncertainties, two EDPs with different sizes (a body EDP and a head EDP) were used for the ρ(e) calibration. Each acquired lookup table was applied to two radiotherapy plans designed using the XiO TPS with the superposition algorithm for an anthropomorphic phantom. The first radiotherapy plan was for an oral cavity tumor and the second was for a lung tumor. RESULTS In both treatment plans, the performance of the ΔHU-ρ(e) conversion was superior to that of the conventional HU-ρ(e) conversion in terms of the reliability of dose calculations. Especially, for the oral tumor plan, which dealt with dentition and bony structures, treatment planning with the HU-ρ(e) conversion exhibited apparent discrepancies between the dose distributions and dose-volume histograms (DVHs) of the body-EDP and head-EDP calibrations. In contrast, the dose distributions and DVHs of the body-EDP and head-EDP calibrations coincided with each other almost perfectly in the ΔHU-ρ(e) conversion for 100-140 kV/Sn. The difference between the V100s (the mean planning target volume receiving 100% of the prescribed dose; a DVH parameter) of the body-EDP and head-EDP calibrations could be reduced to less than 1% using the ΔHU-ρ(e) conversion, but exceeded 11% for the HU-ρ(e) conversion. CONCLUSIONS The ΔHU-ρ(e) conversion can be implemented for currently available TPSs without any modifications or extensions. The ΔHU-ρ(e) conversion appears to be a promising method for providing an accurate and reliable inhomogeneity correction in treatment planning for any ill-conditioned scans that include (i) the use of a calibration EDP that is nonequivalent to the patients body tissues, (ii) a mismatch between the size of the patient and the calibration EDP, or (iii) a large quantity of high-density and high-atomic-number tissue structures.

Salvage endoscopic submucosal dissection in patients with local failure after chemoradiotherapy for esophageal squamous cell carcinoma.

Abstract Objective. For locoregional failure after chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC), salvage esophagectomy and endoscopic mucosal resection have disadvantages, such as a high morbidity rate and a high local recurrence rate, respectively. The aim of this study was to clarify the efficacy of salvage endoscopic submucosal dissection (ESD) for locoregional failure of CRT. Methods. A total of 19 lesions in 19 patients were treated with salvage ESD; 15 lesions were local recurrences at the primary site and 4 lesions were residual. All lesions were intramucosal or submucosal tumors without metastases. A case-control study was retrospectively evaluated to clarify whether the clinical outcomes of salvage ESD were equivalent to those of control primary ESD. Results. No significant differences were observed between salvage ESD and primary ESD in short-term outcomes, including procedure time. For salvage ESD, the complete en bloc resection rate was 94.7% (18 of 19), and no severe complications were observed. At a median follow up of 54.6 (range: 5–98) months after salvage ESD, the local recurrence rate was 0%. However, three patients (15.8%) died due to lymph node and distant metastases and six patients (31.5%) died from other diseases, including radiation pneumonitis, pyothorax or respiratory failure with no recurrence of ESCC. The 3-year overall survival rate for all 19 patients was 74%. Conclusions. ESD represents an acceptable treatment option for recurrent or residual ESCC because of its improvement in local control, when local failure after CRT is limited to the submucosal layer without metastases.

An esophageal squamous cell carcinoma patient with high serum granulocyte-colony stimulating factor level: report of a case

We present herein a case of a patient who was clinically diagnosed as having a granulocyte-colony stimulating factor (G-CSF)-producing tumor on the basis of the close correlation of the hematological parameters with the tumor status and his high serum G-CSF level. A 76-year-old male patient underwent transthoracic radical esophagectomy for advanced carcinoma of the lower esophagus. His leukocyte count and serum G-CSF level were markedly high at 24 260/μl and 134 pg/ml, respectively, before the operation. By immunohistochemical staining of the resected tumor, focal but obvious expression of G-CSF was demonstrated in the cytoplasm of cancer cells, and neutrophilic infiltration was histologically observed in adjacent struma of the tumor invasion front. After surgery, the leukocyte count decreased to a nearly normal level but increased again when the disease recurred in the pleura and lymph nodes 5 months later. Although palliative chemoradiotherapy decreased the leukocyte count to a normal level transiently, leukocyte count again markedly increased when metastatic disease occurred. The leukocyte count reached 78 060/μl the day before the patient died.

Risk factors for enlargement of cardiac silhouette on chest radiography after radiotherapy for esophageal cancer.

PurposeTo evaluate the incidence and risk factors of enlargement of cardiac silhouette on chest radiographs after radiotherapy for esophageal cancer.Materials and methodsWe analyzed 67 patients with esophageal cancer who received external beam radiation therapy with a total dose of ≥50 Gy and were followed for ≥6 months. Sixteen patients received radiation alone, and the remaining 51 received chemoradiotherapy. The difference between the cardiothoracic ratio (CTR) on the pretreatment chest radiograph and that on the posttreatment radiograph with maximum cardiac silhouette for each patient was used for the analysis.ResultsThe average maximum increase in CTR for the entire group was 4.5%, which was statistically significant. Only the area of the cardiac silhouette in the initial radiation field was a significant risk factor for enlargement of the cardiac silhouette. Pericardial effusions were observed in all patients who underwent computed tomography with severe enlargement of the cardiac silhouette.ConclusionThe CTR value significantly increased after radiotherapy for esophageal cancer. Radiation-induced pericardial effusion may be the main cause of enlargement of the cardiac silhouette. The irradiated cardiac area was the only significant risk factor for enlargement of the cardiac silhouette; the use of chemotherapy was not.

Concurrent chemoradiotherapy using low-dose continuous infusion of 5-fluorouracil for postoperative regional lymph node recurrence of esophageal squamous cell carcinoma

BackgroundRadiotherapy plays an important role in salvaging patients who suffer locoregional recurrence; however, it displays poor prognosis. Because concurrent chemoradiotherapy offers superior treatment results compared to radiotherapy alone in patients with localized esophageal cancer, to improve survival rates, we treated patients displaying postoperative regional lymph node recurrence of esophageal squamous cell carcinoma using radiotherapy combined with protracted low-dose continuous infusion of 5-fluorouracil (5-FU).MethodsBetween January 1992 and December 2001, 14 patients with postoperative regional lymph node recurrence of esophageal squamous cell carcinoma were treated with concurrent chemoradiotherapy. Radiotherapy was delivered at 1.8–2.0 Gy/day, for a total dose of 56–70 Gy (median, 60 Gy). Chemotherapy was administered 5 days/week as continuous infusion of 5-FU (250–300 mg/m2) for at least 5 weeks. Median follow-up time was 27 months.ResultsTwelve patients demonstrated partial response, and 2 patients displayed stable disease. Response rate was therefore 86% (12/14). In-field recurrence occurred in 3 patients. Involved lymph nodes that recurred in the irradiation field were ≥40 mm in maximum diameter and invaded into the surrounding normal tissues. Local progression-free rate at 2 years was 72%. As an initial failure, 6 patients displayed out-field recurrence. Disease progression-free rate at 2 years was 42%. Overall survival rates at 1 and 2 years were 85% and 57%, respectively.ConclusionsConcurrent chemoradiotherapy using low-dose continuous infusion of 5-FU was effective for patients with postoperative regional lymph node recurrence of esophageal squamous cell carcinoma. Close follow-up is crucial, and further investigation is required to prevent out-field recurrence.

Definitive chemoradiotherapy with low-dose continuous 5-fluorouracil reduces hematological toxicity without compromising survival in esophageal squamous cell carcinoma patients

Background and purpose To compare chemoradiotherapy (CRT) with low-dose continuous 5-fluorouracil (5FU) to CRT with 5FU+cisplatin (CDDP) for esophageal squamous cell carcinoma (ESCC) in a retrospective cohort study. Methods and materials We reviewed the cases of Stage I–IV ESCC patients who underwent definitive CRT in 2000–2014. Concomitant chemotherapy was one of the three regimens: (1) high-dose intermittent 5FU and CDDP (standard-dose FP: SDFP), (2) low-dose continuous 5FU and CDDP (LDFP), or (3) low-dose continuous 5FU (LD5FU). The general selection criteria for chemotherapy were: SDFP for patients aged <70 yrs; LDFP for those aged 70–74 yrs; LD5FU for those aged ≥75 yrs or with performance status (PS) ≥3. Propensity scores were derived with chemotherapy (LD5FU vs. 5FU+CDDP) as the dependent variable. Results In a multivariate analysis, chemotherapy (LD5FU vs. SDFP, p = .24; LDFP vs. SDFP, p = .52) did not affect the overall survival (OS). LD5FU caused significantly less grade 3–4 leukopenia (9%) compared to SDFP (47%) and LDFP (44%) (p < .001). In a propensity-matched analysis, LD5FU affected neither OS (HR 1.06; 95%CI 0.55–2.05; p = .87) nor progression-free survival (HR 0.95, 95%CI 0.50–1.81; p = .87). Conclusion CRT with low-dose continuous 5FU may be a less toxic option for elderly ESCC patients.

Respiratory gating and multifield technique radiotherapy for esophageal cancer

PurposeTo investigate the effects of a respiratory gating and multifield technique on the dose-volume histogram (DVH) in radiotherapy for esophageal cancer.Methods and materialsTwenty patients who underwent four-dimensional computed tomography for esophageal cancer were included. We retrospectively created the four treatment plans for each patient, with or without the respiratory gating and multifield technique: No gating-2-field, No gating-4-field, Gating-2-field, and Gating-4-field plans. We compared the DVH parameters of the lung and heart in the No gating-2-field plan with the other three plans.ResultIn the comparison of the parameters in the No gating-2-field plan, there are significant differences in the Lung V5Gy, V20Gy, mean dose with all three plans and the Heart V25Gy–V40Gy with Gating-2-field plan, V35Gy, V40Gy, mean dose with No Gating-4-field plan and V30Gy–V40Gy, and mean dose with Gating-4-field plan. The lung parameters were smaller in the Gating-2-field plan and larger in the No gating-4-field and Gating-4-field plans. The heart parameters were all larger in the No gating-2-field plan.ConclusionThe lung parameters were reduced by the respiratory gating technique and increased by the multifield technique. The heart parameters were reduced by both techniques. It is important to select the optimal technique according to the risk of complications.

SU-E-T-392: A Sensitivity Analysis for Evaluating Dosimetric Impact of MLC Modeling Parameter Accuracy On IMRT Treatment Plans

PURPOSE To quantify and evaluate the dosimetric impact of MLC modeling parameter accuracy on IMRT treatment plans by performing a sensitivity analysis. METHODS Physician-approved 8 prostate and 4 head-and-neck IMRT treatment plans in which 7 and 9 fields dynamic MLC technique was utilized respectively were retrospectively analyzed. The dose re-calculation was performed with Eclipse treatment planning system (ver.8.9, Varian Medical Systems) after MLC modeling parameters such as leaf transmission factor (LTF) and dosimetric leaf gap (DLG) were manually shifted from the original value. The change in DVH parameters (PTV D95%, rectum wall D25% and bladder wall D35% for prostate cases; PTV D95%, parotid gland mean dose and spinal canal maximum dose for head-and-neck cases) and point doses were plotted as a function of errors in MLC modeling parameters and the dosimetric impact was quantified by sensitivity (slope of an approximate linear function). The 2D map of dose sensitivity to LTF and DLG were created and overlaid onto CT image of the patient using MATLAB software (ver.8.2.0.701, MathWorks). RESULTS The changes in all analyzed DVH parameters had almost linear relationship with errors in LTF and DLG. The sensitivities of DVH parameters for head-and-neck cases were higher than prostate cases overall. For prostate cases, sensitivities of DVH parameters to DLG were higher than LTF and the opposite results were obtained for head-and-neck cases. According to the 2D map, LTF and DLG had high dose sensitivity around PTV edge especially at the overlap between PTV and rectum for a prostate case. The region of high dose sensitivity to LTF was more blurred and widely scattered than DLG. CONCLUSION The dosimetric impact of MLC modeling parameter accuracy on IMRT treatment plans were successfully quantified by a sensitivity analysis of DVH parameters and a 2D map of dose sensitivity overlaid onto CT image of patients.