Treatment strategy for early-stage esophageal cancer.

Approximately 90% of esophageal cancers in Japan are squamous cell carcinomas, and they are often detected at earlier stages in Japan than in Western countries; superficial esophageal cancer without lymph node or distant metastasis comprises one-third of all esophageal cancers in Japan. Endoscopic resection is a minimally invasive treatment for superficial esophageal cancer; however, the risk of regional lymph node recurrence is negligible when it invades the submucosal layer or lymphovasculature. In such cases, surgical treatment is necessary to control regional lymph node recurrences, although the physical burdens and potential complications cannot be overlooked. Recently, clinical trials in Japan have shown promising clinical outcomes of organ preservation strategies. One strategy is initially performing endoscopic resection for superficial esophageal cancer, assessing the risk of lymph node metastasis based on pathological diagnosis for endoscopically resected specimens, and subsequently considering additional therapy (e.g., observation or prophylactic chemoradiotherapy)-another strategy aimed to cure superficial esophageal cancer through definitive chemoradiotherapy alone. The safety and efficacy of the two strategies have been evaluated in clinical trials, which showed that both organ preservation strategies are comparable to surgery in terms of overall survival. However, challenges include improving the accuracy of pretreatment endoscopic diagnosis and decreasing the local-regional recurrence after chemoradiotherapy. This review provides an overview of the latest standard treatment for early-stage esophageal cancer and its future perspectives.

A phase III randomized controlled trial comparing local field with additional prophylactic irradiation in chemoradiotherapy for clinical-T1bN0M0 esophageal cancer: ARMADILLO trial (JCOG1904).

Chemoradiotherapy has been considered as one of the standard treatment options for clinical T1bN0M0 esophageal squamous cell carcinoma with organ preservation. However, 20% of patients develop locoregional recurrence after chemoradiotherapy, which requires salvage treatment including salvage surgery and endoscopic resection. Salvage surgery can cause complications and treatment-related death. Interestingly, chemoradiotherapy with elective nodal irradiation has been reported to reduce the locoregional recurrence of advanced esophageal squamous cell carcinoma. Hence, we are conducting a clinical trial to confirm whether modified chemoradiotherapy with elective nodal irradiation was superiority to that without elective nodal irradiation for the patients with cT1bN0M0 esophageal squamous cell carcinoma. The primary endpoint is major progression-free survival, defined as the time from randomization to the date of death or disease progression, excluding successful curative resection through salvage endoscopic resection. We plan to enroll 280 patients from 54 institutions over 4 years. This trial has been registered in the Japan Registry of Clinical Trials (jRCTs031200067).

Adjuvant treatments for locally advanced differentiated thyroid cancer: a nationwide survey in Japan.

The role of adjuvant external-beam radiotherapy (EBRT) for locally advanced differentiated thyroid cancer (DTC) is controversial because of the lack of prospective data. To prepare for a clinical trial, this study investigated the current clinical practice of adjuvant treatments for locally advanced DTC. A survey on treatment selection criteria for hypothetical locally advanced DTC was administered to representative thyroid surgeons of facilities participating in the Japan Clinical Oncology Group Radiation Therapy Study Group. Of the 43 invited facilities, surgeons from 39 (91%) completed the survey. For R1 resection or suspected residual disease, 26 (67%) facilities administered high-dose (100-200 mCi) radioactive iodine (RAI), but none performed EBRT. For R2 resection or unresectable primary disease, 26 (67%) facilities administered high-dose RAI and 7 (18%) performed adjuvant treatments, including EBRT. For complete resection with nodal extra-capsular extension, 13 (34%) facilities administered high-dose RAI and 1 (3%) performed EBRT. For unresectable mediastinal lymph node metastasis, 31 (79%) facilities administered high-dose RAI and 5 (13%) performed adjuvant treatments, including EBRT. Adjuvant EBRT was not routinely performed mainly because of the lack of evidence for efficacy (74%). Approximately 15% of the facilities routinely considered adjuvant EBRT for DTC with R2 resection or unresectable primary or lymph node metastasis disease. Future clinical trials will need to optimize EBRT for these patients.

A case of a pregnant woman with locally advanced cervical esophageal cancer treated with definitive chemoradiotherapy.

The information of definitive radiotherapy for a pregnant woman with malignancy was limited; however, it was reported to be potentially feasible with minimal risks. We performed definitive chemoradiotherapy for a pregnant woman with locally advanced cervical esophageal cancer. Feasibility of radiotherapy and safety of fetus were confirmed by the phantom study estimating fetal dose, and monitoring it in each radiotherapy session. The planned chemoradiotherapy completely eradicated esophageal cancer while preserving her laryngopharyngeal function. A female infant was delivered by cesarian section after planned chemoradiotherapy, and she grew without any apparent disorders 2 years after chemoradiotherapy. Chemoradiotherapy might be one of the treatment options for a pregnant woman with cervical esophageal cancer especially wishing the preservation of laryngopharyngeal function.

A Single-Arm Confirmatory Study of Definitive Chemoradiation Therapy Including Salvage Treatment for Clinical Stage II/III Esophageal Squamous Cell Carcinoma (JCOG0909 Study).

PURPOSE: Definitive chemoradiotherapy (CRT) is the standard treatment for patients with locally advanced esophageal cancer (EC) who refuse surgery as the initial therapy. However, poor survival, a high incidence of late toxicities, and severe complications after salvage surgery remain issues to be resolved. This single-arm multicenter trial (JCOG0909) aimed to confirm the efficacy of CRT modifications, including salvage treatment for reducing CRT-related toxicities and facilitating salvage treatment for improved survival. METHODS AND MATERIALS: Patients with clinical stage II/III EC (International Union Against Cancer sixth edition, non-T4) were eligible. Chemotherapy comprised cisplatin (75 mg/m2 on days 1 and 29) and 5-fluorouracil (1000 mg/m2/d on days 1-4 and 29-32). Radiation therapy was administered at a total dose of 50.4 Gy. Good responders received 1 to 2 additional cycles of chemotherapy. For residual or recurrent disease, salvage endoscopic resection or salvage surgery was performed based on specific criteria. The primary endpoint was 3-year overall survival (OS). The calculated sample size was 95 patients, with a 1-sided alpha of 5% and a power of 80%. The expected and threshold 3-year OS were 55% and 42%, respectively. RESULTS: Overall, 96 patients were enrolled, and 94 were included in the efficacy analysis. A complete response was achieved in 55 patients (59%). Salvage endoscopic resection and salvage surgery were performed in 5 (5%) and 25 patients (27%), respectively. R0 resection by salvage surgery was achieved in 19 patients (76%). Five patients (20%) showed grade 3 or 4 early operative complications, and 9 patients (9.6%) showed grade 3 late toxicities during the long-term follow-up. The 3-year OS was 74.2% (90% confidence interval, 65.9%-80.8%). CONCLUSION: The combination of definitive CRT and salvage treatment has lower CRT-related toxicities and yields good OS, thus making it a promising novel treatment option for patients with locally advanced EC.

Association of volumetric-modulated arc therapy with radiation pneumonitis in thoracic esophageal cancer.

The lung volume receiving low-dose irradiation has been reported to increase in volumetric-modulated arc radiotherapy (VMAT) compared with three-dimensional conformal radiotherapy (3DCRT) for thoracic esophageal cancer, which raises concerns regarding radiation pneumonitis (RP) risk. This single institutional retrospective cohort study aimed to explore whether VMAT for thoracic esophageal cancer was associated with RP. Our study included 161 patients with thoracic esophageal cancer, of whom 142 were definitively treated with 3DCRT and 39 were treated with VMAT between 2008 and 2018. Radiotherapy details, dose-volume metrics, reported RP risk factors and RP incidence were collected. The RP risk factors were assessed via multivariate analysis. Dose-volume analysis showed that VMAT delivered more conformal dose distributions to the target volume (P < 0.001) and reduced V30 Gy of heart (57% vs 41%, P < 0.001) but increased V5 Gy (54% vs 41%, P < 0.001) and V20 Gy (20% vs 17%, P = 0.01) of lungs compared with 3DCRT. However, the 1-year incidence rates of RP did not differ between the two techniques (11.3% in 3DCRT vs 7.7% in VMAT, P = 0.53). The multivariate analysis suggested that the presence of interstitial lung disease (ILD) (P = 0.01) and V20 Gy of lungs ≥20% (P = 0.008) were associated with RP. Conclusively, VMAT increased the lung volume receiving low to middle doses irradiation, although this might not be associated with RP. Further studies are needed to investigate the effect of using VMAT for delivering conformal dose distributions on RP.

Preoperative chemoradiotherapy for locally advanced low rectal cancer using intensity-modulated radiotherapy to spare the intestines: a single-institutional pilot trial.

The irradiated volume of intestines is associated with gastrointestinal toxicity in preoperative chemoradiotherapy for rectal cancer. The current trial prospectively explored how much of the irradiated volume of intestines was reduced by intensity-modulated radiotherapy (IMRT) compared with 3-dimensional conformal radiotherapy (3DCRT) and whether IMRT might alleviate the acute gastrointestinal toxicity in this population. The treatment protocol encompassed preoperative chemoradiotherapy using IMRT plus surgery for patients with clinical T3-4, N0-2 low rectal cancer. IMRT delivered 45 Gy per 25 fractions for gross tumors, mesorectal and lateral lymph nodal regions, and tried to reduce the volume of intestines receiving 15 Gy (V15 Gy) < 120 cc and V45 Gy ≤ 0 cc, respectively, while keeping target coverage. S-1 and irinotecan were concurrently administered. Acute gastrointestinal toxicity, rates of clinical downstaging, sphincter preservation, local regional control (LRC) and overall survival (OS) were evaluated. Twelve enrolled patients completed the chemoradiotherapy protocol. The volumes of intestines receiving medium to high doses were reduced by the current IMRT protocol compared to 3DCRT; however, the predefined constraint of V15 Gy was met only in three patients. The rate of ≥ grade 2 gastrointestinal toxicity excluding anorectal symptoms was 17%. The rates of clinical downstaging, sphincter preservation, three-year LRC and OS were 75%, 92%, 92% and 92%, respectively. In conclusion, preoperative chemoradiotherapy using IMRT for this population might alleviate acute gastrointestinal toxicity, achieving high LRC and sphincter preservation; although further advancement is required to reduce the irradiated volume of intestines, especially those receiving low doses.

Chemoradiotherapy for fistula-related perianal squamous cell carcinoma with Crohn's disease.

The reports of chemoradiotherapy for anal squamous cell carcinoma with Crohn's disease are few. Severe toxicity related to radiotherapy is concerned in patients with inflammatory bowel disease. We report a case of chemoradiotherapy for locally advanced fistula-related perianal squamous cell carcinoma in a patient with long-standing Crohn's disease which was controlled by a maintenance therapy. The patient completed standard chemoradiotherapy using intensity-modulated radiotherapy without severe toxicity, and achieved complete remission. Standard chemoradiotherapy using intensity-modulated radiotherapy may be feasible and effective treatment for this population when Crohn's disease is controlled.

Definitive radiotherapy for secondary esophageal cancer after allogeneic hematopoietic stem cell transplantation.

The reports for secondary esophageal cancer treated by radiotherapy or chemoradiotherapy is few, however they potentially yield a cure for esophageal cancer. We report a case of definitive radiotherapy for a patient with secondary locally advanced unresectable esophageal cancer after hematopoietic stem cell transplantation for acute myeloid leukemia. Definitive radiotherapy for the current patient was completed with acceptable toxicity despite the poor general condition with long-term chronic graft-versus-host disease. Radiotherapy may be the definitive treatment for this population unfit for concurrent chemotherapy or surgery.

Reducing variability among treatment machines using knowledge-based planning for head and neck, pancreatic, and rectal cancer.

PURPOSE: This study aimed to assess dosimetric indices of RapidPlan model-based plans for different energies (6, 8, 10, and 15 MV; 6- and 10-MV flattening filter-free), multileaf collimator (MLC) types (Millennium 120, High Definition 120, dual-layer MLC), and disease sites (head and neck, pancreatic, and rectal cancer) and compare these parameters with those of clinical plans. METHODS: RapidPlan models in the Eclipse version 15.6 were used with the data of 28, 42, and 20 patients with head and neck, pancreatic, and rectal cancer, respectively. RapidPlan models of head and neck, pancreatic, and rectal cancer were created for TrueBeam STx (High Definition 120) with 6 MV, TrueBeam STx with 10-MV flattening filter-free, and Clinac iX (Millennium 120) with 15 MV, respectively. The models were used to create volumetric-modulated arc therapy plans for a 10-patient test dataset using all energy and MLC types at all disease sites. The Holm test was used to compare multiple dosimetric indices in different treatment machines and energy types. RESULTS: The dosimetric indices for planning target volume and organs at risk in RapidPlan model-based plans were comparable to those in the clinical plan. Furthermore, no dose difference was observed among the RapidPlan models. The variability among RapidPlan models was consistent regardless of the treatment machines, MLC types, and energy. CONCLUSIONS: Dosimetric indices of RapidPlan model-based plans appear to be comparable to the ones based on clinical plans regardless of energies, MLC types, and disease sites. The results suggest that the RapidPlan model can generate treatment plans independent of the type of treatment machine.

Nonsurgical Management Following Local Resection for Early Rectal Cancer in Patients with High-risk Factors: A Single-institute Experience.

OBJECTIVE: Additional surgery is considered for patients at high risk for lymph node metastasis (LNM) after local resection for early rectal cancer. Several factors are considered as indications for additional surgery, although there are currently no definitive criteria. This study aimed to clarify the need for additional surgery based on the number of risk factors for LNM and to evaluate the significance of submucosal invasion on recurrence. METHODS: Patients with early rectal cancer harboring risk factors for LNM who underwent local resection between March 2005 and December 2016 were retrospectively analyzed. Associations among the number of risk factors, prognosis, and additional treatment after local resection were investigated. RESULTS: A total of 29 eligible patients were classified into the surgery (n = 10), chemoradiotherapy (n = 7), and no-additional-treatment (NAT, n = 12) groups. Among the 29 patients, 15 patients (52%) with only one risk factor did not relapse. The NAT group harbored fewer risk factors for LNM, and 8 of the 12 patients (67%) had only deep submucosal invasion. Local recurrence occurred in one patient in the chemoradiotherapy group. The estimated 5-year overall survival rates were 88.9%, 75.0%, and 81.5% in the surgery, chemoradiotherapy, and NAT groups, respectively. There were no disease-specific deaths in the overall cohort. CONCLUSIONS: In the present study, no recurrence occurred in patients who did not receive additional surgery with deep submucosal invasion as the only risk factor. A multicenter investigation is necessary to confirm the safety of nonsurgical options.

Association of Chemoradiotherapy With Thoracic Vertebral Fractures in Patients With Esophageal Cancer.

Importance: The association of chemoradiotherapy (CRT) with a thoracic vertebral fracture in patients with esophageal cancer is unknown. Objective: To determine whether CRT is associated with thoracic vertebral fractures in patients with esophageal cancer. Design, Setting, and Participants: This retrospective cohort study included patients with clinical stages I to III thoracic esophageal cancer who visited the Kyoto University Hospital, Kyoto, Japan, from January 1, 2007, to December 31, 2013. Data were analyzed from April 6, 2018, to June 4, 2020. Exposures: Chemoradiotherapy (CRT group) or surgery or endoscopic treatment (non-CRT group). Main Outcomes and Measures: The main outcome of this study was the cumulative incidence rate of thoracic vertebral fractures in 36 months. The incidence rate was calculated taking censoring into account. Possible risk factors, including CRT, were explored in the multivariable analysis. The association of irradiated doses with fractured vertebrae was also evaluated. Results: A total of 315 patients (119 for the CRT group and 196 for the non-CRT group) were included. The median age of patients was 65 (range, 32-85) years. Fifty-six patients (17.8%) were female and 259 (82.2%) were male. The median observation time was 40.4 (range, 0.7-124.1) months. Thoracic vertebral fractures were observed in 20 patients (16.8%) in the CRT group and 8 patients (4.1%) in the non-CRT group. The 36-month incidence rate of thoracic vertebral fractures was 12.3% (95% CI, 7.0%-19.1%) in the CRT group and 3.5% (95% CI, 1.3%-7.5%) in the non-CRT group (hazard ratio [HR], 3.41 [95% CI, 1.50-7.73]; P = .003). The multivariable analysis showed that the HR of the thoracic vertebral fracture in the CRT group to non-CRT group was 3.91 (95% CI, 1.66-9.23; P = .002) with adjusting for sex, 3.14 (95% CI, 1.37-7.19; P = .007) with adjusting for age, and 3.10 (95% CI, 1.33-7.24; P = .009) with adjusting for the history of vertebral or hip fractures. The HR of the thoracic vertebral fracture for a 5-Gy increase in the mean radiation dose to the single vertebra was 1.19 (95% CI, 1.04-1.36; P = .009). Conclusions and Relevance: This study found that chemoradiotherapy was associated with thoracic vertebral fractures in patients with esophageal cancers. A reduced radiation dose to thoracic vertebrae may decrease the incidence of fractures.

Therapy-Related Acute Myeloid Leukemia 2 Months after Chemoradiotherapy for Esophageal Cancer: A Case Report.

Therapy-related acute myeloid leukemia (AML) is a rare but potentially fatal adverse event caused by chemotherapy or radiotherapy. Herein we report a patient diagnosed with therapy-related AML 2 months after chemoradiotherapy for esophageal cancer. A 61-year-old man with dysphagia was diagnosed with locally advanced esophageal cancer with para-aortic lymph node metastasis. Laboratory blood test did not reveal any abnormality except mild macrocytic anemia. To alleviate dysphagia due to malignant esophageal stenosis, the patient underwent concurrent chemoradiotherapy of 60 Gy in 30 fractions with cisplatin and 5-fluorouracil at a local area in thoracic esophagus. Dysphagia alleviated during chemoradiotherapy; however, pancytopenia did not recover after the completion of chemoradiotherapy, and general fatigue with fever developed 13 weeks after the last day of chemoradiotherapy. To rule out hematological malignancy, bone marrow biopsy was performed. The bone marrow smear and flow cytometry analysis indicated the development of AML. Chromosomal test revealed a complex karyotype, suggesting that AML was associated with myelodysplastic syndrome. The patient died 1 month after the diagnosis of therapy-related AML. Thus, the findings indicate that therapy-related AML may develop during the acute phase of chemoradiotherapy and bone marrow biopsy is necessary when prolonged pancytopenia exists after chemoradiotherapy.

A Case Report of a Solitary Pelvic Mass Proven to Be a Lymph Nodal Metastasis from Anal Cancer.

A solitary pelvic-wall lymph nodal metastasis can be mistaken as a primary malignancy when a primary tumor has not been diagnosed. We report the case of a 72-year-old woman with a solitary left pelvic-wall mass that was finally proven to be a left internal iliac lymph nodal metastasis from anal cancer. No signs of the primary tumor had been initially found by general screening using computed tomography, colonoscopy, pelvic magnetic resonance imaging, and gynecological/urological examination; however, squamous cell carcinoma was detected by surgical biopsy of the left pelvic-wall mass. Additional 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) showed focal accumulations in the left pelvic mass and the anal canal. A biopsy of the induration in the anal canal led to the diagnosis of anal cancer, clinical T2N2M0, and stage IIIB (UICC-TNM 7th ed.), which was indicated for definitive chemoradiotherapy. Two months after completing a definitive chemoradiotherapy for anal cancer, a fixed induration developed under the surgical wound along with the surgical tract of the biopsy site. Physical examination and 18F-FDG-PET/computed tomography led to the clinical diagnosis of unresectable surgical tract recurrence of anal cancer. The patient underwent palliative treatment and died 14 months after the diagnosis of the surgical tract recurrence. In conclusion, anal cancer may present as a solitary pelvic mass without any anal symptoms. To evaluate the solitary pelvic mass, 18F-FDG-PET/computed tomography, along with digital examination, will probably help in establishing an accurate diagnosis. Anal cancer must be considered during the differential diagnosis of a solitary pelvic-wall mass for a correct diagnosis and to avoid unnecessary procedures.

Adaptive radiotherapy in locally advanced esophageal cancer with atelectasis: a case report.

BACKGROUND: To the best of our knowledge, no study has reported mediastinal shift accompanied with obstructive atelectasis due to bulky primary esophageal tumor components treated with adaptive radiotherapy and concurrent chemotherapy. CASE PRESENTATION: Here we report the case of a 65-year-old male patient diagnosed with locally advanced thoracic esophageal squamous cell cancer, clinical T4bN1M0, stage IVA. Bronchoscopy and computed tomography (CT) revealed an almost complete obstruction of the lumen of the left bronchus due to compression by bulky primary esophageal tumor components. On admission, the patient presented with dyspnea and decreased arterial oxygen saturation. Chest radiography and CT on admission revealed mediastinal shift with left atelectasis, as opposed to findings from the chest radiography performed 26 days before admission. Because of the patient's overall good condition, we recommended definitive chemoradiotherapy instead of palliative bronchial stent placement. After obtaining the patient's consent, chemoradiotherapy was initiated on the following day and it comprised three-dimensional conformal radiotherapy with 60 Gy in 30 fractions with concurrent administration of cisplatin and 5-fluorouracil. During chemoradiotherapy, tumor location was monitored with cone-beam CT and chest radiography. Chemoradiotherapy on day 8 revealed no evidence of the mediastinal shift. CT simulation was reperformed to adjust the radiotherapy fields to account for geometrical changes induced by the absence of the mediastinal shift. Subsequently, the mediastinal shift and bronchial obstruction did not recur during the course of chemoradiotherapy. The patient completed the planned radiotherapy with concurrent and adjuvant chemotherapy, and no non-hematological grade ≥ 3 adverse events were observed. Complete response was confirmed 7 months after initiating chemoradiotherapy. Currently, no disease recurrence, dysphagia, or respiratory symptoms have been reported at 13 months after initiating chemoradiotherapy. CONCLUSIONS: In this study, a bulky primary esophageal tumor caused mediastinal shift due to ipsilateral bronchial obstruction. The close follow-up for monitoring resolution of the mediastinal shift during the course of chemoradiotherapy enabled adequate dose delivery to targets, thus reflecting the geometrical changes induced by the absence of the mediastinal shift. Adaptive radiotherapy technique was crucial for favorable patient outcomes in this challenging clinical situation.

Qualitative and Quantitative Analysis of Posttreatment Strategy After Endoscopic Resection for Patients with T1 Colorectal Cancer at High Risk of Lymph Node Metastasis.

BACKGROUND: Although endoscopic resection is increasingly performed to treat submucosal invasive colorectal cancer (T1CRC), approximately 10% are at risk of lymph node metastasis. The Japanese Society for Cancer of the Colon and Rectum guideline indicates that the following risk factors should be considered when deciding whether to perform additional surgical resection with lymph node dissection: depth of T1 invasion, lymphovascular invasion, poor histological grade, and budding grade 2/3. However, there is little information about the prognosis of T1CRC patients, or factors to consider when deciding subsequent treatment of high-risk T1CRC. METHODS: This retrospective mixed method study was conducted using electronic medical records at Kyoto University Hospital between February 2005 and February 2015. Participants were T1CRC patients at risk of lymph node metastasis with at least one of the above four risk factors. They were assigned either careful follow-up (FU) or additional surgery (AS) through shared decision-making. To identify factors affecting decision-making in the FU group, we performed qualitative content analysis of electronic medical records. The prognosis of the groups was compared using the Kaplan-Meier method and the log-rank test. RESULTS: Of 161 T1CRC patients, 18 were included in the FU group and 19 in the AS group. The median follow-up time was 39.5 (range 23-126) months for the FU group and 62 (range 22-141) months for the AS group. Factors considered in selecting FU were advanced age, comorbidities, the sole presence of the "depth" risk factor, and lower rectal cancer. For AS, the risk factors cited in the guideline were considered. There was one recurrent case in each group during the research period. There were no significant differences in overall survival, cause-specific survival, or recurrence-free survival between the groups. CONCLUSIONS: Age, comorbidities, and lower-rectal cancer location were considered in deciding posttreatment strategy among high-risk T1CRC patients, alongside with positive vertical margin, depth, lymphovascular invasion, poor histologic grade, and budding. During the research period, there was no prognostic difference between the FU and AS groups.

A Case Report of Locally Advanced Anal Cancer with Solitary Cutaneous Nodular Metastasis in the Ipsilateral Labia Majora Treated with Definitive Chemoradiotherapy.

Cutaneous metastasis from anal cancer is rare at the initial diagnosis. There is a dearth of information on definitive treatment for anal cancer with cutaneous metastasis. We report the case of a 63-year-old female with locally advanced anal cancer and solitary cutaneous nodular metastasis in the right labia majora identified at the initial diagnosis that was successfully treated with definitive chemoradiotherapy. She arrived at our hospital with complaints of an enlarging perineal itching nodule. Genital and rectal examination detected an anal tumor with perineal and rectal invasion. The biopsy specimen indicated it was a squamous cell carcinoma that was accompanied by right inguinal and external iliac lymph nodal metastases and solitary cutaneous nodular metastasis in the ipsilateral labia majora. She was diagnosed with anal cancer, clinical T3N1M1, stage IV (UICC-TNM 7th). She had good performance status and effective organ function. She received definitive chemoradiotherapy with irradiation fields that included the primary tumor, pelvic lymph nodal metastases, and solitary cutaneous genital metastasis. After completing the planned treatment, all tumors vanished without recurrences at 42 months after treatment. In conclusion, patients with locally advanced anal cancer may suffer genital cutaneous metastasis that develops with lymphatic drainage from the anus to the inguinal lymph nodes. Anal cancer with solitary genital cutaneous nodular metastasis can be considered as a local-regional disease and can be treated with chemoradiotherapy. Chemoradiotherapy achieved a cure in our case.

Phase III study of tri-modality combination therapy with induction docetaxel plus cisplatin and 5-fluorouracil versus definitive chemoradiotherapy for locally advanced unresectable squamous-cell carcinoma of the thoracic esophagus (JCOG1510: TRIANgLE).

A randomized phase III trial commenced in Japan in February 2018. Definitive chemoradiotherapy (CRT) with cisplatin plus 5-fluorouracil is the current standard treatment for locally advanced unresectable esophageal carcinoma. The purpose of this study is to confirm the superiority of induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (DCF) followed by conversion surgery or definitive CRT over definitive CRT alone for overall survival (OS) in patients with locally advanced unresectable squamous-cell carcinoma of thoracic esophagus. A total of 230 patients will be accrued from 47 Japanese institutions over 4.5 years. The primary endpoint is OS, and the secondary endpoints are progression-free survival, complete response rate of CRT, response rate of DCF, adverse events of DCF and CRT, late adverse events and surgical complications. This trial has been registered at the Japan Registry of Clinical Trials as jRCTs031180181.

Intensity-modulated radiotherapy for cervical esophageal squamous cell carcinoma without hypopharyngeal invasion: dose distribution and clinical outcome.

Hypopharyngeal invasion would be a key finding in determining the extent of the irradiation fields in patients with cervical esophageal squamous cell carcinoma (CESCC). This study aimed to investigate the clinical outcomes of chemoradiotherapy using simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) omitting upper cervical lymph nodal irradiation in CESCC without hypopharyngeal invasion, and the dosimetric superiority of SIB-IMRT to 3D conformal radiotherapy (3DCRT). We retrospectively identified 21 CESCC patients without hypopharyngeal invasion [clinical Stage I/II/III/IV (M1LYM); 3/6/5/7] (UICC-TNM 7th edition) who underwent chemoradiotherapy using SIB-IMRT between 2009 and 2015. SIB-IMRT delivered 60 Gy to each primary tumor and the metastatic lymph nodes, and 48 Gy to elective lymph nodal regions, including Levels III and IV of the neck, supraclavicular, and upper mediastinal lymphatic regions, in 30 fractions. The overall survival rate, locoregional control rate, and initial recurrence site were evaluated. 3DCRT plans were created to perform dosimetric comparisons with SIB-IMRT. At a median follow-up of 64.5 months, the 5-year locoregional control and overall survival rates were 66.7% and 53.4%, respectively. Disease progressed in eight patients: all were locoregional progressions and no patients developed distant progression including upper cervical lymph nodal regions as initial recurrence sites. The planning study showed SIB-IMRT improved target coverage without compromising the dose to the organs at risk, compared with 3DCRT. In conclusion, omitting the elective nodal irradiation of the upper cervical lymph nodes was probably reasonable for CESCC patients without hypopharyngeal invasion. Locoregional progression remained the major progression site in this population.