Publications by authors named "Jun Itami"

189 Publications

Why not de-intensification for uterine cervical cancer?

Gynecol Oncol 2021 Jul 19. Epub 2021 Jul 19.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

Objective: The majority of uterine cervical cancer is known to be related to human papillomavirus (HPV), and HPV-related tumors are known to be radio-sensitive. In the management of HPV-related oropharyngeal cancer, de-intensification of treatment has been attempted; however, no such attempt is performed in the management of cervical cancer. The aim of this study was to identify a group of patients who can safely be treated by de-escalated treatment intensity.

Methods: From the Asian international multi-institutional retrospective study involving 13 Japanese, one Thailand, and one Korean institutions based on 469 patients, squamous cell carcinoma (Scc), tumor reduction ratio ≥29%, tumor size before brachytherapy ≤4 cm, and total treatment time (TTT) <9 weeks were identified as factors having an influence on local control. Based on these findings, low-risk patients having these four factors were extracted, and treatment outcomes categorized in 10 Gy increment of CTV D were compared.

Results: Among 469 patients, 162 patients (34.5%) met the criteria of low-risk group, and 63, 41, 43, and 15 patients were categorized in CTV D 50-60 Gy, 60-70 Gy, 70-80 Gy, and >80 Gy, respectively. While 4-y progression-free survival ranged from 66 to 80%, 4-y local control was consistently over 90% in every dose group. Rectum and bladder D and incidence of late adverse events decreased as CTV D decreased.

Conclusions: The low-risk patients achieved favorable local control with CTV D <80 Gy. A personalized treatment strategy based on tumor response could also be adopted for cervical cancer.
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http://dx.doi.org/10.1016/j.ygyno.2021.07.021DOI Listing
July 2021

Feasibility of conversion thoracoscopic esophagectomy after induction therapy for locally advanced unresectable esophageal squamous cell carcinoma.

Jpn J Clin Oncol 2021 Aug;51(8):1225-1231

Department of Esophageal Surgery, National Cancer Center Hospital, Tokyo, Japan.

Background: Recently, patients with cT4b esophageal cancer often require conversion surgery following induction therapy, for which the standard procedure is open esophagectomy. However, thoracoscopic esophagectomy, including thoracoscopic esophagectomy in the prone position, is increasingly used. We compared short-term outcomes of thoracoscopic esophagectomy and open esophagectomy in this setting.

Methods: We retrospectively analyzed 14 patients who underwent thoracoscopic esophagectomy, and 10 who underwent open esophagectomy, for locally advanced unresectable esophageal cancer after induction therapy between March 2007 and July 2020.

Results: The two groups did not significantly differ in patient background. Median total and thoracic surgical times were both significantly longer for open esophagectomy than for thoracoscopic esophagectomy. Median blood loss was also greater in the open esophagectomy group than in the thoracoscopic esophagectomy group. The thoracoscopic esophagectomy group also had significantly shorter median chest drain duration; and lower C-reactive protein levels on the second and third postoperative days. The two groups did not significantly differ in total complications or postoperative hospital stay.

Conclusions: Thoracoscopic esophagectomy is as safe and feasible as open esophagectomy for conversion surgery after induction therapy for locally advanced unresectable esophageal squamous cell carcinoma.
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http://dx.doi.org/10.1093/jjco/hyab085DOI Listing
August 2021

Distribution of genetic alterations in high-risk early-stage cervical cancer patients treated with postoperative radiation therapy.

Sci Rep 2021 May 19;11(1):10567. Epub 2021 May 19.

Department of Radiation Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Somatic genetic alteration analysis was performed for post-hysterectomy high-risk early-stage uterine cervical cancer patients who underwent post-operative radiation therapy. Post-operative radiation therapy was performed for patients with pathological features of pelvic lymph node metastasis, parametrium invasion, or positive vaginal margin, which corresponded to the post-operative high-risk category. DNA was extracted from paraffin-embedded surgical specimens, and 50 somatic hotspot genetic alternations were detected using Ion AmpliSeq Cancer Hotspot Panel. The existence of actionable mutation was assessed based on OncoKB evidence level > 3A. Between January 2008 and November 2019, 89 patients who underwent abdominal radical hysterectomy followed by post-operative radiation therapy were identified. The follow-up period for living patients was 82.3 months (range 9.3-153.9), and the 5-year relapse-free survival and overall survival rates were 72.6% and 85.9%, respectively. The most frequently detected somatic mutation was PIK3CA (26 [29.2%] patients); however, no prognostic somatic genetic alterations were identified. Actionable mutations were detected in 30 (33.7%) patients. Actionable mutations were detected in approximately one-third of patients, suggesting that precision medicine can be offered to patients with post-operative high-risk uterine cervical cancer in the near future.
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http://dx.doi.org/10.1038/s41598-021-90139-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134569PMC
May 2021

Initial Experience of Intentional Internal High-Dose Policy Volumetric Modulated Arc Therapy of Neck Lymph Node Metastases ≥ 2 cm in Patients With Head and Neck Squamous Cell Carcinoma.

Front Oncol 2021 27;11:651409. Epub 2021 Apr 27.

Department of Radiation Therapy in National Cancer Center Hospital, Tokyo, Japan.

Background And Purpose: Most locoregional recurrences after definitive radiotherapy for head and neck squamous cell carcinoma (HNSCC) develop "in-field." Dose escalation while sparing organs at risk can be a good solution for improving local control without increasing adverse effects. This study investigated the safety and effectiveness of volumetric modulated arc therapy (VMAT) using intentionally internal high-dose policy (IIHDP) to treat neck lymph node metastases (NLNM) ≥ 2 cm in HNSCC patients.

Materials And Methods: We analyzed 71 NLNM from 51 HNSCC patients who had received definitive radiotherapy to treat NLNM ≥ 2 cm using the VMAT technique in our institution between February 2017 and August 2019. Thirty-seven NLNM from 25 patients were treated using IIHDP VMAT (group A), and 34 NLNM from 27 patients were treated with homogeneous-dose distribution policy (HDDP) VMAT (group B). One patient with three NLNM had one lymph node assigned to group A and the other two to group B. Adverse events and local recurrence-free survival (LRFS) was compared between the two groups.

Results: In the median follow-up period of 527 days, there were no significant differences between the groups in terms of dermatitis or mucositis ≥ grade 2/3, but LRFS was significantly longer in group A (p = 0.007). In the Cox regression analysis after adjustment for the propensity score, group A also showed an apparently superior LFRS.

Conclusion: Our initial experience of IIHDP VMAT suggested that IIHDP VMAT to treat HNSCC neck lymph node metastases measuring ≥ 2 cm was feasible and possibly led to better local control than HDDP VMAT.
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http://dx.doi.org/10.3389/fonc.2021.651409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112241PMC
April 2021

Neutron flux evaluation model provided in the accelerator-based boron neutron capture therapy system employing a solid-state lithium target.

Sci Rep 2021 Apr 13;11(1):8090. Epub 2021 Apr 13.

Division of Research and Development for Boron Neutron Capture Therapy, National Cancer Center Exploratory Oncology Research & Clinical Trial Center, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan.

An accelerator-based boron neutron capture therapy (BNCT) system employing a solid-state Li target can achieve sufficient neutron flux for treatment although the neutron flux is reduced over the lifetime of its target. In this study, the reduction was examined in the five targets, and a model was then established to represent the neutron flux. In each target, a reduction in neutron flux was observed based on the integrated proton charge on the target, and its reduction reached 28% after the integrated proton charge of 2.52 × 10 mC was delivered to the target in the system. The calculated neutron flux acquired by the model was compared to the measured neutron flux based on an integrated proton charge, and the mean discrepancies were less than 0.1% in all the targets investigated. These discrepancies were comparable among the five targets examined. Thus, the reduction of the neutron flux can be represented by the model. Additionally, by adequately revising the model, it may be applicable to other BNCT systems employing a Li target, thus furthering research in this direction. Therefore, the established model will play an important role in the accelerator-based BNCT system with a solid-state Li target in controlling neutron delivery and understanding the neutron output characteristics.
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http://dx.doi.org/10.1038/s41598-021-87627-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044165PMC
April 2021

Treatment results of radiotherapy to both the prostate and metastatic sites in patients with bone metastatic prostate cancer.

J Radiat Res 2021 May;62(3):511-516

Department of Radiation Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Although systemic therapy is the standard treatment for metastatic prostate cancer, a randomized controlled trial showed radiotherapy to the prostate improved overall survival of metastatic prostate cancer patients with the low metastatic burden. Additionally, a randomized phase II trial showed that metastasis-directed therapy for oligo-recurrent prostate cancer improved androgen-deprivation therapy (ADT)-free survival. Therefore, administering radiotherapy to both prostate and metastatic regions might result in better outcomes. Thus, we report the treatment results of radiotherapy to both prostate and metastatic regions. Our institutional database was searched for patients who received radiotherapy to the prostate and metastatic regions. We summarized patient characteristics and treatment efficacy and performed statistical analysis to find possible prognostic factors. A total of 35 patients were included in this study. The median age was 66 years, and the median initial prostate-specific antigen (PSA) level was 32 ng/ml. The Gleason score was 7 in 10 patients, 8 in 13 patients, and 9 in 12 patients. The median radiotherapy dose was 72 Gy to the prostate and 50 Gy to the metastatic bone region. The 8-year overall survival, cause-specific survival, progression-free survival, and freedom from biochemical failure rate were 81, 85, 53, and 57%. Among the 35 patients, 12 were disease-free even after ADT was discontinued. In selected patients with metastatic prostate cancer, ADT and radiotherapy to the prostate and metastatic sites were effective. Patients with good response to ADT may benefit from radiotherapy to both prostate and metastatic regions.
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http://dx.doi.org/10.1093/jrr/rraa056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127693PMC
May 2021

Usefulness of Simple Original Interstitial Lung Abnormality Scores for Predicting Radiation Pneumonitis Requiring Steroidal Treatment After Definitive Radiation Therapy for Patients With Locally Advanced Non-Small Cell Lung Cancer.

Adv Radiat Oncol 2021 Jan-Feb;6(1):100606. Epub 2020 Oct 31.

Department of Radiotherapy in National Cancer Center Hospital, Tokyo, Japan.

Purpose: Adjuvant durvalumab has become a standard treatment after chemoradiation therapy for patients with locally advanced non-small cell lung cancer (LA-NSCLC). Accordingly, predicting radiation pneumonitis (RP) requiring steroidal treatment (steroid-RP) is of utmost importance because steroidal administration is reported to weaken the effectiveness of immunotherapy. However, grade 2 RP was used as an index of RP in previous studies, but it is an ambiguous definition because it includes not only steroid-RP but also a mild cough requiring only a cough medicine. Therefore, in this study, steroid-RP was used for evaluating RP, and the purpose of this study was to investigate predictive factors of steroid-RP, including original simple interstitial lung abnormality scores (ILASs).

Methods And Materials: A total of 145 patients with LA-NSCLC who received definitive radiation therapy (DRT) in our institution from January 2014 to May 2017 were identified. Original ILASs, performance status, age, respiratory function, Brinkman index, concurrent administration of chemotherapy, and dose-volume histogram metrics of the lung were analyzed to evaluate their association with steroid-RP. Additionally, 3 diagnostic radiologists evaluated the patients' pre-DRT chest computed tomography images and determined the simple ILASs. ILASs were rated as follows: 0: none; 1: abnormality without honeycombing (ground-glass attenuation, fine reticular opacity, and microcysts); and 2: honeycombing.

Results: The median follow-up period was 729 days. Thirty-one patients (21.4%) experienced steroid-RP. In the univariate analysis, lung V5/V10/VS5, Brinkman index, and ILASs were significant predictive factors of steroid-RP. Additionally, multivariate analysis including Brinkman index ≥840, lung V5 ≥37%, and an ILAS ≥1 revealed that only an ILAS ( = .001) was an independent predictive factor of steroid-RP.

Conclusions: The original simple ILAS was an easy-to-use tool and a significant predictive factor of steroid-RP in DRT in patients with LA-NSCLC.
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http://dx.doi.org/10.1016/j.adro.2020.10.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897760PMC
October 2020

Relationship between cervical esophageal squamous cell carcinoma and human papilloma virus infection and gene mutations.

Mol Clin Oncol 2021 Feb 30;14(2):41. Epub 2020 Dec 30.

Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.

Cervical esophageal squamous cell carcinoma (CESCC) is rare, accounting for 5% of all esophageal carcinomas. Several diagnostic and predictive markers have been studied. However, to the best of our knowledge, no biomarker is known to determine patient management except the clinical stage. The present study aimed to evaluate whether human papilloma virus (HPV) infection, epidermal growth factor receptor (EGFR) and its pathway-related gene mutations, known to be sensitive biomarkers of oropharyngeal carcinomas, could be used as biomarkers for the prediction of the prognosis of patients with CESCC. The present retrospective study included patients with CESCC who received chemoradiotherapy or surgery. HPV infection and the genomic status of , , , and of each tumor sample from patients with CESCC were analyzed by hybridizations (ISH) and PCR methods, respectively. The present study included 33 patients with CESCC (male/female, 29/4; median age, 62 years; age range, 41-86 years; clinical stage I/II/III/IV, 2/6/10/15). The present study detected HPV in one patient (3.0%) by ISH and PCR. Concerning the investigation of and its pathway-related gene mutations, the present study detected 15.1% of , 6.0% of , 3.5% of , 3.0% of and 3.0% for mutations, with no significant relationship between any gene mutations and the clinical prognostic factors. The HPV-infected patient did not exhibit any gene mutations. The present study indicated that HPV infection, EGFR and its pathway-related gene mutations rarely exist in patients with CESCC. The relationship between these biomarkers and the prognosis in patients with CESCC is still unclear.
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http://dx.doi.org/10.3892/mco.2020.2205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788557PMC
February 2021

Tensor Regression-based Model to Investigate Heterogeneous Spatial Radiosensitivity After I-125 Seed Implantation for Prostate Cancer.

In Vivo 2021 Jan-Feb;35(1):489-497

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

Background/aim: We established a data-driven method for extracting spatial patterns of dose distribution associated with radiation injuries, based on patients with prostate cancer who underwent iodine-125 (I-125) seed implantation.

Patients And Methods: Seventy-five patients underwent I-125 seed implantation for prostate cancer. We modeled the severity of lower urinary tract symptoms (LUTS) to be estimated using a linear model, which is formulated as an inner product between the dose distribution and voxel-wise radiosensitivity inside the prostate. For the estimation, tensor regression based on a low-rank decomposition with generalized fused lasso penalty was applied.

Results: The spatial distribution of was visually assessed. Positive parameters appeared dominantly in the region close to the urethra and the prostate base.

Conclusion: Our tensor regression-based model can predict intra-organ radiosensitivity in a data-driven manner, providing a compelling parameter distribution associated with the development of LUTS after I-125 seed implantation for prostate cancer.
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http://dx.doi.org/10.21873/invivo.12283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880750PMC
June 2021

Prognostic Value of Epithelial Cell Adhesion Molecules in T1-2N0M0 Glottic Cancer.

Laryngoscope 2021 07 28;131(7):1522-1527. Epub 2020 Dec 28.

Division of Radiation Oncology, Department of Radiology, Showa University School of Medicine, Tokyo, Japan.

Objective: This is an ancillary study of a multi-institutional randomized non-inferiority phase III trial of accelerated fractionation (AF) versus standard fractionation (SF) radiation therapy for T1-2N0M0 glottic cancer (JCOG0701). Biopsy specimens of tumors from the patients enrolled in the JCOG0701 are collected and the association between clinical outcomes and histopathologic features such as expression of epithelial cell adhesion molecule (EpCAM), p53, and p16 were investigated.

Methods: Five slices of undyed slides from biopsy specimens were sent to the National Cancer Center Hospital and all the specimens were assessed for the expression of EpCAM, p53, and p16. The primary objective was to investigate the association between 3-year progression-free survival (PFS) and expression of EpCAM, p53, and p16.

Results: A total of 88 out of 370 patients were enrolled in this ancillary study. The 3-year PFS for tumors with strong expression of EpCAM was 70.6% (95% CI 43.1%-86.6%), while that of tumors without strong expression of EpCAM was 77.5% (95% CI 65.9%-85.5%) with no remarkable difference between groups (P = .67). Likewise, there was no significant difference in 3-year PFS between tumors regardless of p53 or p16 status. However, in a subgroup analysis for 17 patients with a strong expression of EpCAM, AF showed better 3-year PFS than SF (100% vs 54.5%, P = .07).

Conclusions: From the current study, it could not be concluded that EpCAM, p16, and p53 were prognostic factors for early-stage glottic cancer after primary radiation therapy. AF might be an appropriate fractionation for tumors with a strong expression of EpCAM.

Level Of Evidence: 3 Laryngoscope, 131:1522-1527, 2021.
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http://dx.doi.org/10.1002/lary.29348DOI Listing
July 2021

A dosimetric and centeredness comparison of the conventional and novel endobronchial applicators: A preliminary study.

Brachytherapy 2021 Mar-Apr;20(2):467-477. Epub 2021 Jan 19.

Department of Radiation Oncology, National Cancer Center Hospital, Chuo City, Tokyo, Japan.

Purpose: This study compared the applicator position relative to the tracheal wall and dosimetric parameters between conventional and novel applicators among patients receiving endobronchial brachytherapy (EBBT) for intratracheal tumors.

Methods And Materials: Data from 7 patients who received EBBT for intratracheal tumors were retrospectively analyzed; 4 and 3 patients were treated with conventional (2-wing) or novel (5-wing) applicators, respectively. Applicator centrality was evaluated using the distance between the center of the trachea and main bronchus (TMB) lumen and path of source (L). Dosimetric parameters, including plans normalized to D of the TMB = 45 Gy (normalized plan), were compared between the applicators.

Results: The mean and maximum values of L in cases of the 2-wing applicator group were approximately 5.0 mm and 10.0 mm, respectively. In the novel applicator group, the corresponding values were approximately 3.0 and 6.0 mm, respectively. In the normalized plan of the 2-wing applicator group, the ranges of median V of clinical target volume (CTV) and D of the TMB in all cases were 23.0-91.9% and 66.3-153.1 Gy, respectively. In the 5-wing applicator group, the corresponding values were 69.2-83.8% and 60.4-84.5 Gy, respectively.

Conclusions: In the 5-wing applicator group, the range was narrow in all dose-volume parameters except for D of the TMB. Compared to the conventional applicator, the 5-wing applicator can give a stable dose to the CTV and can reduce the maximum dose of the TMB. This suggests that stable EBBT can be given to any patient using the 5-wing applicator.
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http://dx.doi.org/10.1016/j.brachy.2020.11.005DOI Listing
January 2021

Dosimetric effect of the intestinal gas of online adaptive stereotactic body radiotherapy on target and critical organs without online electron density correction for pancreatic cancer.

Br J Radiol 2021 Mar 5;94(1119):20200239. Epub 2021 Feb 5.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

Objective: This study aimed to assess the dosimetric effect of intestinal gas of stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) on target and critical organs for pancreatic cancer without online electron density correction (EDC).

Methods: Thirty pancreatic cancer patients who underwent online SMART were selected for this study. The treatment time of each stage and the total treatment time were recorded and analyzed. The concerned dose-volume parameters of target and organs-at-risk (OAR) were compared with and without an intestinal gas EDC using the Wilcoxon-signed rank test. Analysis items with value < 0.05 were considered statistically significant. The relationships between dosimetric differences and intestinal gas volume variations were investigated using the Spearman test.

Results: The average treatment time was 82 min, and the average EDC time was 8 min, which accounted for 10% of the overall treatment time. There were no significant differences in CTV (GTV), PTV, bowel, stomach, duodenum, and skin ( > 0.05) with respect to dose volume parameters. For the of gastrointestinal organs ( = 0.03), the mean dose of the liver ( = 0.002) and kidneys ( = 0.03 and = 0.04 for the left and right kidneys, respectively), there may be a risk of slight overestimation compared with EDC, and for the of the spinal cord ( = 0.02), there may be a risk of slight underestimation compared with EDC. A weak correlation for in the PTV and in the duodenum was observed.

Conclusion: For patients with similar inter-fractional intestinal gas distribution, EDC had little dosimetric effects on the of all GI organs and dose volume parameters of target in most plans.

Advances In Knowledge: By omitting the EDC of intestinal gas, the online SMART treatment time can be shortened.
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http://dx.doi.org/10.1259/bjr.20200239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011255PMC
March 2021

The use of hyperbaric oxygen to treat actinic rectal fistula after SpaceOAR use and radiotherapy for prostate cancer: a case report.

BMC Urol 2020 Dec 14;20(1):196. Epub 2020 Dec 14.

Department of Radiation Therapy, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo, Japan.

Background: In definitive radiation therapy for prostate cancer, the SpaceOAR® System, a hydrogel spacer, is widely used to decrease the irradiated dose and toxicity of rectum. On the other hand, periprostatic abscesses formation and rectal perforation are known as rare adverse effects of SpaceOAR. Nevertheless, there is a lack of reports clarifying the association between aggravation of abscesses and radiation therapy, and hyperbaric oxygen therapy (HBOT) is effective for a peri-SpaceOAR abscess and rectal perforation.

Case Presentation: We report a case of a 78-year-old high-risk prostate cancer patient. After SpaceOAR insertion into the correct space, he started to receive external beam radiation therapy (EBRT). He developed a fever, perineal pain and frequent urination after the completion of EBRT, and the magnetic resonance imaging (MRI) revealed a peri-SpaceOAR abscess. Scheduled brachytherapy was postponed, administration of antibiotics and opioid via intravenous drip was commenced, and transperineal drainage was performed. After the alleviation of the abscess, additional EBRT instead of brachytherapy was performed with MRI-guided radiation therapy (MRgRT). On the last day of the MRgRT, perineal pain reoccurred, and MRI and colonoscopy detected the rectal perforation. He received an intravenous antibiotics drip and HBOT, and fully recovered from the rectal perforation.

Conclusions: Our report indicates that EBRT can lead to a severe rectum complication by causing inflammation for patients with a peri-SpaceOAR abscess. Furthermore, HBOT was effective for the peri-SpaceOAR abscess and rectal perforation associated with EBRT.
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http://dx.doi.org/10.1186/s12894-020-00767-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737272PMC
December 2020

Image-guided interstitial brachytherapy boost for keratinizing squamous cell carcinoma of inferior wall of the nasopharynx.

BJR Case Rep 2020 Dec 21;6(4):20200005. Epub 2020 Aug 21.

Department of Radiation Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan.

High-dose-rate interstitial brachytherapy (HDR-ISBT) is relatively rarely applied for the head and neck cancer because of its anatomical complexity and difficulty of applicator placement. However, its dose distribution is more confined even better than intensity-modulated radiation therapy (IMRT) and can deliver a higher dose while sparing surrounding normal tissues. In this case report, the effectiveness of HDR-ISBT as a boost following IMRT for keratinizing squamous cell carcinoma of nasopharynx was presented. A 76-year-old female who suffered from cT3N0M0 keratinizing squamous cell carcinoma of the nasopharynx was treated with definitive concurrent chemoradiation therapy involving IMRT. However, physical examination and laryngoscope fibre finding showed evident residual tumour at 60 Gy of IMRT, then, boost HDR-ISBT was proposed. After delivering 66 Gy of IMRT, CT image-guided HDR-ISBT 4 Gy in a single fraction was performed under local anaesthesia and sedation. MRI taken 5 months after HDR-ISBT showed remarkable shrinkage of the primary tumour. After HDR-ISBT, the remaining session of IMRT was delivered from the next day until 70 Gy in 35 fractions. It was demonstrated that boost HDR-ISBT combined with IMRT for keratinizing squamous cell carcinoma of the nasopharynx was performed safely and showed favourable efficacy.
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http://dx.doi.org/10.1259/bjrcr.20200005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709071PMC
December 2020

Transvaginal artificial ascites infusion as a spacer in gynecological brachytherapy: a novel technique.

J Contemp Brachytherapy 2020 Oct 30;12(5):487-491. Epub 2020 Oct 30.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

This is a first paper to report on artificial ascites infusion via vaginal wall for pelvic interstitial brachytherapy. Artificial ascites is commonly used for treating liver tumors, with radiofrequency ablation and percutaneous artificial ascites infusion through the abdominal wall for pelvic brachytherapy has been previously reported by our group. However, the trans-abdominal needle approach under ultrasound guidance is unreliable due to poor visualization resulting in fluid injection into the abdominal wall or mesenterium and the rate of successful artificial ascites infusion was low. Target tumor of the vaginal cuff brachytherapy is usually adjacent to the intestine, and transvaginal artificial ascites infusion under trans-rectal ultrasonography is considered as a rational and simpler method to create a space between target volume and organs at risk, such as intestines or sigmoid colon, by increased visualization of the needle compared to trans-abdominal approach. Here, we report a practical experience of transvaginal artificial ascites infusion.
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http://dx.doi.org/10.5114/jcb.2020.100382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701932PMC
October 2020

Advantages and challenges for noninvasive atrial fibrillation ablation.

J Interv Card Electrophysiol 2020 Oct 26. Epub 2020 Oct 26.

Cardiac Arrhythmia Service, Brigham and Women's Hospital, Boston, MA, USA.

Purpose: Although catheter ablation is an effective therapy for atrial fibrillation (AF), risks remain and improved efficacy is desired. Stereotactic radiotherapy is a well-established therapy used to noninvasively treat malignancies with precision. We sought to evaluate stereotactic arrhythmia radioablation (STAR) as a therapeutic option for treating AF.

Methods And Results: Three cancer patients with drug refractory AF were enrolled. Planning software using 3-D CT of the left atrium was used to design a desired ablation volume encompassing antral circumferential pulmonary vein isolation, roof and floor lines to create a "box" lesion set. After planning, patients were treated in the radioablation suite. STAR was able to deliver the intended radiation dose to the target in all 3 patients. No complications were observed over a follow-up period of 24 months. One patient with paroxysmal AF died from deterioration of cancer. The autopsy revealed evidence of fibroblasts and fibrogenesis in the region of atrial tissues targeted with radioablation. In one of these patients, left atrial posterior wall electrograms recorded from the esophagus before and 3 months after STAR indicated successful electrical isolation.

Conclusions: This is the first report of non-invasive radioablation of the left atrium with demonstration of successful electrical isolation. Although STAR may be safe and effective in delivering ablative energy to the left atrium, further evaluation is warranted regarding effectiveness.
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http://dx.doi.org/10.1007/s10840-020-00904-wDOI Listing
October 2020

The role of local radiotherapy following rituximab-containing chemotherapy in patients with transformed indolent B-cell lymphoma.

Eur J Haematol 2021 Feb 6;106(2):213-220. Epub 2020 Nov 6.

Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.

Objectives: This study aimed to evaluate the outcomes of local radiotherapy (LRT) in patients with histologic transformation (HT) following rituximab-containing chemotherapy.

Methods: We retrospectively analysed 92 patients with biopsy-confirmed HT undergoing rituximab-containing chemotherapy at our institution between 2003 and 2015.

Results: Of the 36 patients with limited-stage disease at diagnosis of HT, 29 (78%) received LRT. The estimated 5-year progression-free survival (PFS) rate was significantly better in patients who underwent LRT than in those who did not (93% and 42%, respectively; P < 0.05). Multivariate analyses employing age, sex, performance status, LRT and treatment response demonstrated that LRT was an independent prognostic factor for PFS (hazard ratio [HR]: 11.8; 95% confidence interval [CI]: 1.28-108.1; P < 0.05). Of the 32 patients who underwent LRT for HT lesion treatment, 31 (97%) did not show disease progression within radiation fields; among them, 27 patients (84%) survived without disease progression during the follow-up period. One patient developed hypothyroidism due to LRT; the others had no acute or late-onset complications of LRT.

Conclusions: Our data support the recommendation of LRT for HT lesion treatment following rituximab-containing chemotherapy in select patients with localised HT, as a rational treatment approach with potentially limited toxicity.
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http://dx.doi.org/10.1111/ejh.13539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894292PMC
February 2021

Radiation protection in radiological imaging: a survey of imaging modalities used in Japanese institutions for verifying applicator placements in high-dose-rate brachytherapy.

J Radiat Res 2021 Jan;62(1):58-66

Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku Fukuoka, Fukuoka, 812-8582, Japan.

Institutional imaging protocols for the verification of brachytherapy applicator placements were investigated in a survey study of domestic radiotherapy institutions. The survey form designed by a free on-line survey system was distributed via the mailing-list system of the Japanese Society for Radiation Oncology. Survey data of 75 institutions between August 2019 and October 2019 were collected. The imaging modalities used were dependent on resources available to the institutions. The displacement of a brachytherapy applicator results in significant dosimetric impact. It is essential to verify applicator placements using imaging modalities before treatment. Various imaging modalities used in institutions included a computed tomography (CT) scanner, an angiography X-ray system, a multi-purpose X-ray system and a radiotherapy simulator. The median total exposure time in overall treatment sessions was $\le$75 s for gynecological and prostate cancers. Some institutions used fluoroscopy to monitor the brachytherapy source movement. Institutional countermeasures for reducing unwanted imaging dose included minimizing the image area, changing the imaging orientation, reducing the imaging frequency and optimizing the imaging conditions. It is worth noting that half of the institutions did not confirm imaging dose regularly. This study reported on the usage of imaging modalities for brachytherapy in Japan. More caution should be applied with interstitial brachytherapy with many catheters that can lead to potentially substantial increments in imaging doses for monitoring the actual brachytherapy source using fluoroscopy. It is necessary to share imaging techniques, standardize imaging protocols and quality assurance/quality control among institutions, and imaging dose guidelines for optimization of imaging doses delivered in radiotherapy should be developed.
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http://dx.doi.org/10.1093/jrr/rraa088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779356PMC
January 2021

Configuration analysis of the injection position and shape of the gel spacer in gynecologic brachytherapy.

Brachytherapy 2021 Jan-Feb;20(1):95-103. Epub 2020 Oct 1.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

Purpose: In this single-institution retrospective study, configuration analysis was performed to determine the optimal location and volume of hyaluronic acid gel spacer injection into the rectovaginal or vesicovaginal septum for effective dose reduction (DR) to the organs at risk (OARs), the rectum and bladder.

Methods And Materials: 70 and 50 intracavitary brachytherapy treatment plans used only vaginal cylinders with gel spacers for the rectal and bladder sides, respectively, whereas 28 did not use spacers. Correlation analysis was performed between the geometrical parameters and injection position of the gel spacers and the 2-cm covering doses of the OARs for each treatment.

Results: A higher DR was predicted for hyaluronic acid gel spacer injection within ±5 mm and ±2.5 mm in the lateral-medial direction from the midpoint on the rectal and bladder sides, and ±10 mm in the cranial-caudal direction from the midpoint on the rectal side. There were correlations between 2-cm covering doses and the gel spacer parameters: the volume on the rectal (p = 0.02) and bladder (p = 0.04) sides; the craniocaudal length on the rectal side (p << 0.05); and ventrodorsad thickness on each OAR (p << 0.05) sides. There was no significant difference in the DR between a volume of ∼10 cm and that of a higher volume (p >> 0.05).

Conclusions: A gel spacer volume of ∼10 cm provides sufficient OAR DR if its gravity point is on the midpoint between the cylinder applicator and OAR, and its craniocaudal length covers the active length of the cylinder applicator.
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http://dx.doi.org/10.1016/j.brachy.2020.08.021DOI Listing
October 2020

Short-term outcomes of induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) in locally advanced nasopharyngeal carcinoma.

Invest New Drugs 2021 Apr 17;39(2):564-570. Epub 2020 Sep 17.

Department of Head and Neck Surgery, National Cancer Center Hospital, Tokyo, Japan.

There is an unmet need for improving survival outcomes of locally advanced nasopharyngeal carcinoma, for example, T4/ N3 stage disease. To this end, we administered induction chemotherapy (IC) with TPF (docetaxel, cisplatin, and fluorouracil) because this stage of disease is associated with a high risk of recurrence and is difficult to control with standard treatments, such as chemoradiotherapy (CRT) alone or CRT followed by adjuvant chemotherapy. The aim of this retrospective single-center study was to clarify the short-term outcomes of locally far-advanced nasopharyngeal carcinoma patients treated with IC-TPF, followed by CRT with cisplatin. Data from 11 patients were extracted from our database, indicating that the overall response rate to IC-TPF, clinical complete response rate after CRT, 1-year progression-free survival, and 1-year overall survival were 73%, 91%, 68%, and 89%, respectively. Hematological toxicity was the most common adverse event reported during IC-TPF with 64% of patients suffering grade 3 or 4 neutropenia, 55% grade 3 or 4 leucopenia and 9% febrile neutropenia. Despite the small number of patients, these data are important because there is a limited number of studies investigating IC-TPF followed by CRT in Japanese patients. This pilot study provides some indication of the short-term effectiveness and toxicity of this therapeutic approach, which may be superior to standard treatments. Long-term follow-up is warranted to assess the effectiveness of IC-TPF in terms of clinical outcome and late-phase toxicity.
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http://dx.doi.org/10.1007/s10637-020-00999-yDOI Listing
April 2021

Clinical outcomes of definitive whole pelvic radiotherapy for clinical lymph node metastatic prostate cancer.

Cancer Med 2020 09 4;9(18):6629-6637. Epub 2020 Aug 4.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

Background: In this study, we aim to present the clinical outcomes of radiotherapy (RT) in clinical pelvic lymph node-positive prostate cancer (cN1) patients. We also analyze the prognostic factors with focus on RT dose escalation to metastatic lymph nodes (LN).

Methods: We retrospectively analyzed the data from cN1 patients who were treated with definitive RT and androgen deprivation therapy (ADT) between June 2004 and February 2016. All patients received localized irradiation to the prostate region and whole pelvis irradiation. Some patients received intensity-modulated radiation therapy with RT dose escalation to metastatic LN. Univariate analyses using log-rank test were performed to find prognostic factors between patient subgroups.

Results: Fifty-one consecutive patients were identified. The median follow-up period for all patients was 88 (range 20-157) months. Primary Gleason pattern and LN RT dose were statistically significant prognostic factors for relapse-free survival (RFS) and distant metastasis-free survival (DMFS). Especially, RT dose escalation (60 Gy or more) to metastatic LN significantly improved RFS and DMFS compared with standard dose RT (4-year RFS 90.6% vs 82.1%, 7-year RFS 90.6% vs 58.0%, P = .015; 4-year DMFS 90.6% vs 82.1%, 7-year DMFS 90.6% vs 62.8%, P = .023). The following factors were all statistically significant for biochemical relapse-free survival (BRFS): T stage, LN RT dose, local RT dose, and ADT duration period. Any significantly different toxicity was not seen for each LN or local RT dose except for the incident rate of grade 2 or more acute urinary retention, which was significantly higher in the higher LN RT dose (60 Gy or more) group by the Chi-square test.

Conclusions: RT dose escalation to metastatic LN in cN1 patients improves BRFS, RFS, and DMFS at 4 and 7 years, without increasing severe adverse events.
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http://dx.doi.org/10.1002/cam4.2985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520291PMC
September 2020

Image-guided interstitial brachytherapy boost for nasopharyngeal carcinoma: technical aspects.

J Contemp Brachytherapy 2020 Jun 30;12(3):294-302. Epub 2020 Jun 30.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

Nasopharyngeal cancer generally responds well to concurrent chemoradiotherapy (CCRT). However, there is a small group of patients who respond poorly to CCRT, and experience local residual tumor or local relapse. Although several attempts have been performed to such a group of patients including re-irradiation with external beam radiation therapy (EBRT) or salvage surgery, clinical results remain unsatisfactory. Intracavitary brachytherapy (ICBT) boost after CCRT with EBRT has been explored, however, its efficacy is limited to those with superficial residual tumors. For those residual tumors thickness with more than 5 mm, interstitial brachytherapy (ISBT) boost would be an appropriate modality of choice. Here, we describe technical aspects of the high-dose-rate interstitial brachytherapy (HDR-ISBT) boost for nasopharyngeal cancer (NPC) patients who responded poorly to the CCRT with EBRT.
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http://dx.doi.org/10.5114/jcb.2020.96874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366018PMC
June 2020

A case report of a patient with bulky uterine cervical neoplasm who achieved complete response with "intentional internal high-dose policy" high-dose-rate interstitial brachytherapy.

Medicine (Baltimore) 2020 Jul;99(27):e20860

Department of Radiation Therapy, National Cancer Center Hospital, Tokyo.

Rationale: Gynecological high-dose-rate (HDR) brachytherapy has progressed for years, but it remains difficult for bulky tumors to be controlled locally. Dose limitations to organs at risk (OARs) are invariably obstacles in increasing the prescription dose. Additionally, it is controversial that the excessive hyperdose sleeve, the volume receiving a dose equal to or greater than twice the reference dose, should be eliminated in gynecological HDR brachytherapy. On the other hand, the technique of simultaneous integrated protection was reported for large hepatocellular carcinoma treatment, and similarly, internal high-dose brachytherapy could be used for treating bulky cervical carcinoma.

Patient Concerns: A 54-year-old female had irregular genital bleeding and lost 13 kg in one year.

Diagnosis: She was diagnosed with T3bN1M0 cervical cancer in another hospital. The transverse diameter of the primary tumor was 10.5 cm.

Interventions: The whole pelvis and para-aortic lymph node were irradiated with a total of 50 Gy in 25 fractions, but the size of the tumor showed only a slight decrease to 8.9 cm. After external beam radiotherapy, first-time high-dose-rate interstitial brachytherapy (HDR-ISBT) was administered without "intentional internal high-dose (IIHD) policy," the technique of high-dose administration to only the inside of the tumor. Considering the rectum dose limitation, in the additional 2 times of brachytherapy, "IIHD policy" HDR-ISBT was applied. In the second and third HDR-ISBT, the percentage of the volume exposed to 200% of the prescribed dose for high-risk clinical target volume increased by 241% and 204% compared with the first HDR-ISBT, while the doses to OARs were not significantly higher than those of the first-time HDR-ISBT.

Outcomes: Complete response was obtained, and no recurrence findings and side effects caused by HDR-ISBT have been detected for 2 years and 9 months.

Lessons: To our knowledge, this is the first report of IIHD HDR-ISBT for bulky cervical cancer. This technique can be the solution for treating bulky cervical cancer.
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http://dx.doi.org/10.1097/MD.0000000000020860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337609PMC
July 2020

How Much Was the Elective Lymph Node Region Covered in Involved-Field Radiation Therapy for Locally Advanced Pancreatic Cancer? Evaluation of Overlap Between Gross Target Volume and Celiac Artery-Superior Mesenteric Artery Lymph Node Regions.

Adv Radiat Oncol 2020 May-Jun;5(3):377-387. Epub 2019 Sep 13.

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

Purpose: The purpose of this study was to investigate the overlaps between gross target volume (GTV) and the celiac artery (CA) and superior mesenteric artery (SMA) lymph node regions and to examine the dose incidentally irradiated to the CA and SMA lymph node regions by involved-field radiation therapy (IFRT) for locally advanced pancreatic cancer (LAPC).

Methods And Materials: Fifty-nine patients who had LAPC without distant metastasis were included. They received IFRT at 50.4 Gy in 28 fractions with 3-dimensional conformal radiation therapy. We calculated the percentages of overlap of GTV in the CA and SMA lymph node regions and examined what cases tend to have an overlap. We also investigated the dose metrics of CA and SMA lymph node regions by IFRT and the frequency of CA or SMA lymph node metastasis after IFRT.

Results: The median GTV volume was 52.2 mL. Median overlap percentages in the CA and SMA lymph node regions were 39.2% and 28.6%, respectively. There was a significant correlation between GTV volume and SMA overlap percentage ( < .001). Although the SMA overlap percentage was higher in the pancreas head ( = .028), the CA overlap percentage was higher in the pancreas body or tail ( = .002). Median mean dose, D95, and minimum dose in the CA lymph node region were 50.1 Gy, 48.7 Gy, and 45.9 Gy, respectively, and those in the SMA lymph node region 49.9 Gy, 47.3 Gy, and 39.2 Gy, respectively. CA lymph node metastases after IFRT were detected in 4 patients (6.8%).

Conclusions: An overlap between GTV and CA-SMA lymph node regions was detected in many patients, and the CA and SMA lymph node regions were irradiated incidentally even by IFRT. Prophylactic lymph node regions might not be necessary in radiation therapy planning of LAPC.
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http://dx.doi.org/10.1016/j.adro.2019.08.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278027PMC
September 2019

Stereotactic body radiation therapy for early-stage non-small-cell lung cancer in octogenarians and older: an alternative treatment.

J Radiat Res 2020 Jul;61(4):586-593

Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan.

Surgery is the standard modality for early-stage I-II non-small-cell lung cancer (NSCLC). Generally, patients who are >80 years old tend to have more comorbidities and inferior physical status than younger patients. Stereotactic body radiation therapy (SBRT) may provide an alternative treatment for this group of patients. Here, we report our experience using SBRT to in the management of early-stage NSCLC in patients >80 years old. Patients aged ≥80 years old who were diagnosed with early-stage NSCLC and treated with definitive lung SBRT from January 2000 to January 2018 were retrospectively analysed. Local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), cancer-specific survival (CSS), progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were analysed for patients >80 years old. A total of 153 patients were included, with a median age of 85 years (range, 80-94). The median follow-up period and OS was 39.8 months (range, 10-101 months) and 76 months, respectively. The 3-year OS, PFS, CSS, RRFS and LRFS were 65.3, 58.0, 75.7, 73.9 and 85.3%, respectively. Radiation pneumonitis grade 0-1, grade 2, grade 3 and grade 4 was observed in 135 (88.2%), 13 (8.5%), 4 (2.61%) and 1 (0.6%) patient(s), respectively. On multivariate analyses, tumor size, pretreatment C-reactive protein (CRP) value, histology and pretreatment physical state were significantly associated with OS. Definitive lung SBRT appears to have high LRFS and OS without causing high-grade radiation-related toxicities in early-stage NSCLC patients who were >80 years old.
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http://dx.doi.org/10.1093/jrr/rraa027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336556PMC
July 2020

Non-invasive quantitative measures of qualitative grading effectiveness as the indices of acute radiation dermatitis in breast cancer patients.

Breast Cancer 2020 Sep 3;27(5):861-870. Epub 2020 May 3.

Appearance Support Center, National Cancer Center Hospital, Tokyo, Japan.

Background: Recent improvement of machinery evaluation for the skin changes in various therapies enabled us to evaluate fine changes quantitatively. In this study, we performed evaluation of the changes in radiation dermatitis (RD) using quantitative and qualitative methods, and verified the validity of the conventional qualitative assessment for clinical use.

Methods: Forty-three breast cancer patients received conventional fractionated radiotherapy to whole breast after breast-conserving surgery. Erythema, pigmentation and skin dryness were evaluated qualitatively, and biophysical parameters of RD were measured using a Multi-Display Device MDD4 with a Corneometer for capacitance, a Tewameter for transepidermal water loss (TEWL), a Mexameter for erythema index and melanin index. Measurements were performed periodically until 1 year.

Results: The quantitative manifestations developed serially from skin erythema followed by dryness and pigmentation. Quantitative measurements detected the effects of irradiation earlier than that of qualitative indices. However, the grades of the domains in RD by qualitative and quantitative assessment showed similar time courses and peak periods. However, no significant correlation was observed between the skin dryness grade and skin barrier function. In contrast to serial increase in pigmentation grades, melanin index showed initial decrease followed by marked increase with significant correlation with pigmentation grades.

Conclusion: Subjectively and objectively measured results of RD were almost similar course and peak points through the study. Therefore, validity of the conventional qualitative scoring for RD is confirmed by the present quantitative assessments. Instrumental evaluations revealed the presence of modest inflammatory changes before radiotherapy and long-lasting skin dryness, suggesting indication of intervention for RD.
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http://dx.doi.org/10.1007/s12282-020-01082-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438338PMC
September 2020

Long-term outcomes of patients with recurrent squamous cell carcinoma of the esophagus undergoing salvage endoscopic resection after definitive chemoradiotherapy.

Surg Endosc 2021 04 30;35(4):1766-1776. Epub 2020 Apr 30.

Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan.

Background: Salvage endoscopic resection (ER) has been reported to be effective for patients with local failure of esophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy (dCRT). This study aimed to evaluate the long-term outcomes of salvage ER for patients with local failure of ESCC and to identify risk factors associated with disease recurrence after salvage ER.

Methods: This study included 45 patients undergoing salvage ER after dCRT during 2000 to 2017. After ER, all patients were required to undergo surveillance esophagogastroduodenoscopy (EGD) once or twice every year, and a computed tomography (CT) examination was repeated every 3 to 6 months. We assessed short-term outcomes and long-term outcomes.

Results: Of the 45 patients in this study, the baseline clinical T stage before dCRT was T1 in 80%, 66% of the patients did not have nodal metastasis. The median time from CRT to the detection of local failure was 11 months (range 2-130 months). The en-bloc resection rate was 46%, and the R0 resection rate was 38%, respectively. Stricture occurred after salvage ER for one case, while adverse events such as bleeding or perforation and ER-related death did not occur. After a median observation period of 57 months, recurrence free survival at 3 years was 58%, overall survival was 72%, and disease specific survival was 81%. In multivariate analysis, clinical N stage before CRT was the only independent risk factor of recurrence after salvage ER (p = 0.04).

Conclusions: Salvage ER might be effective local treatment in patients with local failure after dCRT. For the patients with clinical N stage, frequent surveillance should be performed.
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http://dx.doi.org/10.1007/s00464-020-07571-yDOI Listing
April 2021
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