Prognostic factors associated with the transition in treatment methods for brain metastases from colorectal cancer.

BACKGROUND: Treatment of brain metastases (BMs) from colorectal cancer (CRC) has transitioned with the expansion of indications for stereotactic radiotherapy. Our study aimed to assess changes in prognosis and prognostic factors associated with changes in treatment for BMs from CRC. METHODS: We retrospectively surveyed treatments for and outcomes of BMs from CRC in 208 patients treated during 1997-2018. Patients were divided into two groups according to time of BM diagnosis, i.e., 1997-2013 ("first period") and 2014-2018 ("second period"). We compared overall survival between the periods and assessed how the transition impacted prognostic factors affecting overall survival, including the following prognostic factors such as Karnofsky performance status (KPS), volume-related factors (BM number and diameter), and BM treatment modalities as covariates. RESULTS: Of the 208 patients, 147 were treated in the first period and 61 in the second period. Whole-brain radiotherapy use decreased from 67 to 39% in the second period, and stereotactic radiotherapy use increased from 30 to 62%. Median survival after BM diagnosis improved from 6.1 to 8.5 months (p = 0.0272). Multivariate analysis revealed KPS, control of primary tumor, stereotactic radiotherapy use, and chemotherapy history as independent prognostic factors during the entire observation period. Hazard ratios of KPS, primary tumor control, and stereotactic radiotherapy were higher in the second period, whereas prognostic impact of chemotherapy history before BM diagnosis was similar in both periods. CONCLUSION: Overall survival of patients with BMs from CRC improved since 2014, which can be attributed to advances in chemotherapy and the more widespread use of stereotactic radiotherapy.

Large volume was associated with increased risk of acute non-hematologic adverse events in the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer: preliminary results of prospective phase I/II clinical trial.

OBJECTIVE: This is the preliminary results of a multi-center prospective clinical trial evaluating the feasibility of the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer. METHODS: Patients with FIGO stage IB2, IIA2, IIB, IIIA, IIIB and IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by MRI were eligible. Protocol therapy consisted of 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of hybrid of intracavitary and interstitial and pelvic radiotherapy with central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase I part was that the rate of grade ≥ 3 acute non-hematologic adverse events related to hybrid of intracavitary and interstitial would be <10%. RESULTS: Between October 2015 and October 2019, 74 patients underwent primary registration, with 52 patients eventually proceeding to the secondary registration. The median pretreatment tumor width was 5.7 cm, and FIGO Stages were IB2 10, IIA2 2, IIB 20 and IIIB 20, respectively. The median high-risk clinical target volume D90 was 72.0 Gy (54.8-86.6 Gy, EQD2), rectum D2cc was 53.7 Gy (29.3-80.3 Gy) and bladder D2cc was 69.8 Gy (38.9-84.8 Gy). The rate of grade ≥ 3 non-hematologic adverse events related to hybrid of intracavitary and interstitial was 1.9% (1/52), and 17.3% (9/52) of patients experienced non-hematologic adverse events related to hybrid of intracavitary and interstitial of any grade. In multivariate analysis, high-risk clinical target volume ≥ 35 ml was associated with an increased risk of any grade of acute non-hematologic adverse events related to hybrid of intracavitary and interstitial (P = 0.036). CONCLUSION: The feasibility and reproducibility of hybrid of intracavitary and interstitial were demonstrated from a multi-center prospective clinical trial.

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

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.

Why not de-intensification for uterine cervical cancer?

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 CTVHR D90 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 CTVHR D90 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 D2cc and incidence of late adverse events decreased as CTVHR D90 decreased. CONCLUSIONS: The low-risk patients achieved favorable local control with CTVHR D90 <80 Gy. A personalized treatment strategy based on tumor response could also be adopted for cervical cancer.

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

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.

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

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.

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

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.

Genomic alterations in STK11 can predict clinical outcomes in cervical cancer patients.

OBJECTIVE: Cervical cancer is the fourth most common cause of cancer-related deaths in Asian women, due to its poor prognosis. This study aimed to decipher genomic alteration profiles of a cohort of Japanese cervical cancer patients to understand why certain patients benefited from molecular targeted therapies and their prognostic significance. METHODS: During 2008-2018, 154 cervical cancer patients underwent a potentially curative resection procedure at the National Cancer Center Hospital. Genomic DNA samples were analyzed using Ion AmpliSeq™ Cancer Hotspot Panel v2. Alterations in the copy number of PIK3CA, ERBB2, PTEN, and STK11 were detected using the TaqMan assay. HPV-positive results were confirmed by genomic testing and in situ hybridization assay. RESULTS: The frequency of genomic alterations in PIK3CA (36%), STK11 (16%), PTEN (11%), TP53 (11%), and KRAS (8%) was >5%. KRAS mutations were preferentially detected in patients with adenocarcinomas, and the frequency of PIK3CA mutations in patients with squamous cell carcinomas was higher than that in patients with other histological cancer types. HPV-positive results were observed in 139/154 (90.3%) patients, and TP53 mutants were detected in HPV-negative specimens. In this study, the overall survival of patients with genomic alterations in STK11 was worse than in patients with wild-type STK11 (hazard ratio = 10.6, P = 0.0079) and TCGA dataset (hazard ratio = 2.46, P = 0.029). CONCLUSIONS: More than one-third of Japanese cervical cancer patients exhibit mutations targeted by molecular targeted therapies. We have proposed the prognostic value of STK11 genomic alterations.

Modern development of high-dose-rate brachytherapy.

Brachytherapy is an invasive therapy with placement of radiation source into or near the tumor. The difference between planning target volume and clinical target volume is minimal, and the dose out of the tumor reduces rapidly due to the inverse-square law. High-dose-rate brachytherapy enables three-dimensional image guidance, and currently, tumor dose as well as doses of the surrounding normal structures can be evaluated accurately. High-dose-rate brachytherapy is the utmost precision radiation therapy even surpassing carbon ion therapy. Biological disadvantages of high-dose rate have been overcome by the fractional irradiation. High-dose-rate brachytherapy is indispensable in the definitive radiation therapy of cervical cancer. Also in prostate cancer and breast cancer, high-dose-rate brachytherapy plays a significant role. Brachytherapy requires techniques and skills of radiation oncologists at the time of invasive placement of the radiation source into the tumor area. Education of young radiation oncologists is most urgent and important.

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

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.

Comparison of involved field radiotherapy and elective nodal irradiation in combination with concurrent chemotherapy for T1bN0M0 esophageal cancer.

BACKGROUND: The optimal radiation field of chemoradiation therapy (CRT) for stage I esophageal squamous cell carcinoma (ESCC) is unknown. This retrospective study compared efficacy and safety of two CRT modalities, involved field irradiation (IFI) and elective nodal irradiation (ENI), when treating patients with clinical stage I (T1bN0M0) ESCC. METHODS: Patients had received 60 Gy CRT concurrently with 5-FU and cisplatin between January 2000 and December 2012. The clinical target volume of IFI was limited to the primary tumor plus a 2-cm craniocaudal margin; that of ENI covered the primary tumor plus the field of regional lymph nodes. RESULTS: One hundred and ninety-five patients were selected (IFI group, 78; ENI group, 117). The 5-year overall, cause-specific and progression-free survival rates were 90.5%, 91.6% and 77.6% in the IFI group, and 72.5%, 88.3%, 57.9% in the ENI group, respectively. Of recurrent patients (n = 16 in the IF and n = 33 in the ENI groups) after achieving complete remission, 12 (75%) in the IFI group received definitive salvage therapy, 11 (33%) patients did in the ENI group. More patients died of diseases other than esophageal cancer in the ENI group (n = 29, 25%) than in the IFI group (n = 3, 3.8%). Multivariate analysis identified ENI (HR 3.63 [1.78-7.38], p < 0.001), age ≥ 70 (HR 2.65 [1.53-4.58], p < 0.001) and PS = 1 (HR 2.36 [1.33-4.18], p = 0.003) as poor prognostic factors for OS. CONCLUSIONS: IF irradiation would be better than ENI for the patients with stage I ESCC who received definitive chemoradiotherapy.

Prognostic factors of brain metastases from colorectal cancer.

BACKGROUND: For brain metastases from non-specific primary tumors, the most frequently used and validated clinical prognostic assessment tool is Karnofsky performance status (KPS). Given the lack of prognostic factors of brain metastases from colorectal cancer (CRC) other than KPS, this study aimed to identify new prognostic factors. METHODS: This retrospective cohort study was conducted at a tertiary care cancer center. Subjects were patients with brain metastases from CRC among all patients who received initial treatment for CRC at the National Cancer Center Hospital from 1997 to 2015 (n = 7147). Prognostic clinicopathological variables for overall survival (OS) were investigated. RESULTS: There were 68 consecutive patients with brain metastases from CRC, corresponding to 1.0% of all patients with CRC during the study period. Median survival time was 6.8 months. One-year and 3-year OS rates were 28.0 and 10.1%, respectively. Among the six covariates tested (age, KPS, presence of extracranial metastases, control of primary lesion, number of brain metastases, and history of chemotherapy), multivariate analysis revealed KPS (score ≥ 70), number of brain metastases (1-3), and no history of chemotherapy to be independent factors associated with better prognosis. CONCLUSIONS: In addition to KPS, the number of brain lesions and history of chemotherapy were independent prognostic factors for OS in patients with brain metastases from CRC. An awareness of these factors may help gastrointestinal surgeons make appropriate choices in the treatment of these patients.

A hybrid technique of intracavitary and interstitial brachytherapy for locally advanced cervical cancer: initial outcomes of a single-institute experience.

BACKGROUND: Locally advanced uterine cervical cancer (LAUCC) with lateral tumor extension may not always be covered adequately by conventional intracavitary brachytherapy (ICBT). Hybrid intracavitary and interstitial brachytherapy (HBT) seems to be an effective alternative by improving anatomy-oriented dose optimisation. The purpose of this study was to report initial clinical result for LAUCC treated by HBT. METHODS: Between January 2012 and November 2015, 42 patients with LAUCC (T1b2-4a) were treated with primary radiation therapy including HBT. Patients with distant metastasis other than para-aortic lymph node spread were excluded from this study. A retrospective analysis was performed for toxicity evaluation and oncological outcome calculation. RESULTS: Median follow-up was 23.2 months (range 13.2-71.4). Two-year overall survival, progression free survival, and local control rate were 81.6, 54.4, and 80.2%, respectively. Seven patients experienced local recurrence (16.6%). Of those, five were confined to the uterus and two at the parametria. Late adverse events ≥ grade 3 were seen in 3 patients. CONCLUSIONS: HBT can generate favorable local control in tumors which cannot be adequately covered by ICBT.

Identifying selection criteria for non-radical hysterectomy in FIGO stage IB cervical cancer.

AIM: This retrospective study sought to identify the selection criteria required for a non-radical hysterectomy with minimal parametrectomy in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB invasive cervical cancer. METHODS: Overall, 461 patients with FIGO stage IB cervical cancer who underwent a radical hysterectomy were reviewed clinicopathologically according to pathological tumor size (≤2 cm, >2 - ≤4 cm, and > 4 cm). RESULTS: The pathological parametrial involvement rate in the less than equal to 2 cm group (2%) was significantly lower than in greater than 2-less than equal to 4 cm (13%) or greater than 4 cm (29%) groups (both P < 0.001). The 5-year overall survival rate was significantly higher in the less than equal to 2 cm group (97%, 95% confidence interval [CI] 94-99%) compared with greater than 2-less than equal to 4 cm (90%, 95% CI 94-86%) and greater than 4 cm (70%, 95% CI 79-60%) groups (both P < 0.001). Cox model analysis identified tumor size to be an independent prognostic factor for survival (95% CI 1.33-5.78) and recurrence (95% CI 1.31-5.66) compared to other pathological factors. However, a significant difference between the three groups was not found in rates of Grade 3 or 4 adverse events following radical hysterectomy (P = 0.19). CONCLUSIONS: Tumor size is an independent prognostic factor for survival in patients with FIGO stage IB invasive cervical cancer. This retrospective study suggests that FIGO stage IB patients with a less than equal to 2 cm tumor size are optimal candidates for non-radical hysterectomy with minimal parametrectomy, and without resulting bladder dysfunction.

Gastric mucosal injury and hemorrhage after definitive chemoradiotherapy for locally advanced esophageal cancer.

BACKGROUND: Definitive chemoradiotherapy is one of the treatment options for locally advanced esophageal cancer with curative intent. Esophagitis and pharyngitis are well-known adverse events that occur during chemoradiotherapy, but gastric mucosal injury has been less frequently reported compared to mucositis. Importantly, gastric mucosal injury is not well known, hard to manage, and sometimes fatal. Hence, we examined the clinical characteristics and the incidence of gastric mucosal injury after CRT for esophageal cancer. METHODS: The medical records of patients who received definitive chemoradiotherapy combined with 5-fluorouracil and cisplatin for stage II/III (nonT4) esophageal squamous cell carcinoma from January 2001 to December 2010 at our institute were reviewed retrospectively. RESULTS: We investigated 256 patients in whom, data for endoscopic abdomen examinations were both before and after CRT were available. Gastric mucosal damage was observed in 90 patients (35%) (grade 1/2/3 = 69/18/3). One of the possible risk factors identified in this study was the irradiation dose to abdomen. Compared to patients with cervical esophagus-upper thoracic esophagus tumor location, patients with middle thoracic esophagus-abdominal esophagus tumor location were more likely to develop gastric mucosal damage, although there was no statistically significant difference. CONCLUSIONS: It is important to consider gastric mucosal injury in patients who receive CRT, particularly when the irradiation field includes stomach.

Non-invasive estimation of 10 B-4-borono-L-phenylalanine-derived boron concentration in tumors by PET using 4-borono-2-18 F-fluoro-phenylalanine.

In boron neutron capture therapy (BNCT), 10 B-4-borono-L-phenylalanine (BPA) is commonly used as a 10 B carrier. PET using 4-borono-2-18 F-fluoro-phenylalanine (18 F-FBPA PET) has been performed to estimate boron concentration and predict the therapeutic effects of BNCT; however, the association between tumor uptake of 18 F-FBPA and boron concentration in tumors remains unclear. The present study investigated the transport mechanism of 18 F-FBPA and BPA, and evaluated the utility of 18 F-FBPA PET in predicting boron concentration in tumors. The transporter assay revealed that 2-aminobicyclo-(2.2.1)-heptane-2-carboxylic acid, an inhibitor of the L-type amino acid transporter, significantly inhibited 18 F-FBPA and 14 C-4-borono-L-phenylalanine (14 C-BPA) uptake in FaDu and LN-229 human cancer cells. 18 F-FBPA uptake strongly correlated with 14 C-BPA uptake in 7 human tumor cell lines (r = .93; P < .01). PET experiments demonstrated that tumor uptake of 18 F-FBPA was independent of the administration method, and uptake of 18 F-FBPA by bolus injection correlated well with BPA uptake by continuous intravenous infusion. The results of this study revealed that evaluating tumor uptake of 18 F-FBPA by PET was useful for estimating 10 B concentration in tumors.

Patterns of Relapse after Definitive Chemoradiotherapy in Stage II/III (Non-T4) Esophageal Squamous Cell Carcinoma.

PURPOSE: The purpose of this study was to investigate the utility of surveillance after definitive chemoradiotherapy (dCRT) in patients with squamous cell carcinoma. METHODS: Patients who underwent dCRT for stage II/III (excluding T4) esophageal squamous cell carcinoma were analyzed. First failures following complete response were classified into luminal relapse (LR), regional relapse (RR), distant metastasis (DM), new cancer diagnosed by esophagogastroduodenoscopy (NC-E), and new cancer other than NC-E (NC-O). We focused on LR, RR, and NC-E, and analyzed their frequency, timings and survival outcomes after local treatments. RESULTS: Among 302 patients treated with dCRT, 204 achieved complete response. The number of patients who recurred with LR, RR, DM, NC-E, and NC-O were 28 (14% of 204), 13 (6%), 39 (19%), 34 (17%), and 16 (8%). Ninety-three percent of LRs were diagnosed within 3 years after dCRT, and all RRs were diagnosed within 2 years. Annual odds of NC-E did not decrease over time. Twenty-three patients with LR, 6 with RR, and 32 with NC-E underwent local treatment, and their median overall survivals were 49.2, 19.5, and 108.9 months. CONCLUSION: Surveillance with esophagogastroduodenoscopy may be important in the first 3 years after dCRT to detect LR and to detect NC-E beyond 3 years.

Type of second primary malignancy after achieving complete response by definitive chemoradiation therapy in patients with esophageal squamous cell carcinoma.

BACKGROUND: While the standard treatment for stage II-III (non-T4) esophageal squamous cell carcinoma (ESCC) is neoadjuvant therapy followed by esophagectomy, definitive chemoradiation therapy (dCRT) is an option to treat ESCC patients who reject or may not tolerate surgical treatment. Second primary malignancy (SPM) is a problem for long-term survivors after achieving complete response (CR) by dCRT. METHODS: The source of the subjects in this study was the patients with stage II/III (excluding T4 disease) ESCC (UICC6th) who underwent dCRT from 2000 to 2011 at the National Cancer Center Hospital, Japan. SPM, defined as malignancy newly detected at different site from the initial disease, was checked in patients who achieved CR by the initial dCRT. RESULTS: Among the 285 patients with stage II/III (excluding T4 disease) ESCC who underwent dCRT, 185 patients achieved CR. SPM was detected in 49 patients (median time to developing SPM, 41.5 months), accounting for 19.3% (95% CI 0.137-0.257) as the 5-year cumulative risk of SPM. SPMs were head and neck cancer (n = 12), gastric cancer (n = 12), esophageal cancer (n = 7), lung cancer (n = 5), colon cancer (n = 4), diffuse large B-cell lymphoma (n = 3), bladder cancer (n = 2), small intestinal cancer (n = 1), cholangiocarcinoma (n = 1), malignant melanoma (n = 1), and breast cancer (n = 1). There were no significant differences in baseline characteristics between the patients who developed SPM (n = 49) and others (n = 136). CONCLUSIONS: Because second primary malignancy developed often after achieving CR by dCRT for ESCC, it should be followed carefully.

Intrafraction esophageal motion in patients with clinical T1N0 esophageal cancer.

AIM: To investigate the intrafraction movement of the esophagus using fiducial markers. BACKGROUND: Studies on intrafraction esophageal motion using the fiducial markers are scarce. MATERIALS AND METHODS: We retrospectively analyzed patients with clinical T1N0 esophageal cancer who had received fiducial markers at our hospital between July 2007 and December 2013. Real-Time Position Management System to track the patient's respiration was used, and each patient underwent three-dimensional computed tomography of the resting expiratory and inspiratory level. We used the center of the marker to calculate the distance between the expiratory and inspiratory breath-holds, which were measured with the radiotherapy treatment planning system in three directions: left-right (LR), superior-inferior (SI), and anterior-posterior (AP). The movements at each site were compared with the Kruskal-Wallis analysis and Wilcoxon rank sum test with a Bonferroni correction. RESULTS: A total of 101 patients with 201 fiducial markers were included. The upper, middle and lower thoracic positions had 40, 77, and 84 markers, respectively. The mean absolute magnitudes of the shifts (standard deviation) were 0.18 (0.19) cm, 0.68 (0.46) cm, and 0.24 (0.24) cm in the LR, SI, and AP directions, respectively. From the cumulative frequency distribution, we assumed that 0.35 cm LR, 0.8 cm SI, and 0.3 cm AP in the upper; 0.5 cm LR, 1.55 cm SI, and 0.55 cm AP in the middle; and 0.75 cm LR, 1.9 cm SI, and 0.95 cm AP in the lower thoracic esophagus covered 95% of the cases. CONCLUSIONS: The internal margin based on the site of esophagus was estimated.

Efficacy of radiotherapy for primary tumor in patients with unresectable pancreatic neuroendocrine tumors.

BACKGROUND: Detailed information regarding the clinical efficacy of radiotherapy (RT) for primary tumor in patients with unresectable pancreatic neuroendocrine tumors (pNETs) is unknown. We therefore performed a retrospective study to evaluate the efficacy and safety of RT for primary pancreatic tumors in patients with pNETs. METHODS: We investigated 11 patients with pNETs who received RT to the primary site between January 1997 and June 2015. Seven patients had Grade 2 neuroendocrine tumors (NET-G2) and four had neuroendocrine carcinoma (NEC) according to the 2010 WHO histopathological classification. RESULTS: The tumor response and control rates were 27.2% and 100%, respectively (3: partial response, 8: stable disease). Among patients with NET-G2 tumors, the response rate was 28.5% (2/7 patients) and symptomatic improvement was noted in 33.3% of the patients (1/3 patients). The response rate for patients with NEC were 25% (1/4), one NEC patients with symptoms exhibited symptomatic improvement. The median overall survival and median progression-free survival were 35.9 months and 5.5 months, respectively. Grade 3 diarrhea as an acute toxicity and Grade 3 gastrointestinal hemorrhage as a late toxicity were observed. CONCLUSIONS: RT to the primary cancer site in patients with pNETs was an effective modality for local disease control and the treated patients had good outcomes. If metastatic tumors are under control, RT to the primary site may be beneficial for patients with pNETs.