A Phase II Study of Neoadjuvant Chemoradiotherapy with Docetaxel, Cisplatin and 5-FU Followed by Surgical Resection in the Treatment of Locally Advanced Esophagogastric Junction Cancer and Locally Advanced Esophageal Cancer.

PURPOSE: We conducted a phase II study evaluating chemoradiotherapy in patients with advanced esophageal cancer, using the docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen followed by surgery. The primary purposes of this clinical trial were to assess the efficacy and safety of chemoradiotherapy employing the DCF regimen in the treatment of advanced esophageal cancer. MATERIAL AND METHODS: We enrolled a total of 24 newly diagnosed esophageal cancer patients between April 2015 and November 2017 in this prospective study. The radiotherapy regimen consisted of a total dose of 45 Gy in 25 fractions. The chemotherapy protocol included docetaxel 35 mg/m2 for 1 h on day 1 and day 29, cisplatin 35 mg/m2 for 1 h on day 1 and day 29, and 5-FU 400 mg/m2 for 24 h on day 1-4 and day 29-32. The patients who accepted the re-staging exam should undergo surgery in 4-8 weeks after the completion of radiotherapy. The primary endpoints of this study were disease-free survival (DFS), overall survival (OS), and the evaluation of hematologic toxicity. RESULTS: The study population had a median age of 55.5 years, ranging from 44 to 66, with over 90% of the patients being male. The 5-year DFS was 37.1%, and the 5-year OS was 48.7%. The pathologic complete response rate was 45.8% (11/24). The most common types of toxicity were leukopenia and thrombocytopenia. No grade 3 or greater hematologic toxicity was reported. CONCLUSIONS: The use of the DCF regimen in neoadjuvant chemoradiotherapy followed by surgery demonstrated tolerable toxicity and achieved acceptable DFS and OS outcomes.

The Impact of Deep Inspiration Breath Hold (DIBH) Implementation on the Hybrid Technique in Left-Sided Whole Breast Irradiation: A Dosimetric Characteristic Study of 3D-CRT Hybrid VMAT in DIBH and Free Breathing Conditions, and VMAT in Free Breathing Conditions.

Aim: To investigate the impact of DIBH for heart sparing effect on left sided breast postoperative whole breast irradiation by comparing the dosimetric characteristics of 3D-CRT hybrid VMAT and pure VMAT treatment planning under DIBH condition. Materials and Methods: The primary CT data sets from previously treated left sided early breast cancer were used for pure volumetric arc therapy (VMAT) technique re-planning for the dosimetric characteristics comparison. A treatment plan of 3D-CRT hybrid VMAT technique was re-planned on the free breath (FB) condition for the investigation of the dosimetric characteristics comparison on DIBH condition. The prescribed dose for all the treatment plans was 42.5Gy in 16 fractions. All plans were optimized to cover 100% of the PTV by 95% of prescribed dose. The dosimetric differences among the 3 treatment plans for the 20 patients were analyzed using Wilcoxon signed-rank test, with p value<0.05 considered statistically significant. Results: 3D-CRT hybrid VMAT using DIBH technique yielded the best results on the conformity index (CI) and homogeneity index (HI). By comparing this 3D-CRT hybrid VMAT technique using FB and DIBH technique, the mean heart dose (MHD) was reduced from 5.38Gy to 1.65Gy, respectively (p =0.001) and the left anterior descending coronary artery (LAD)0.03cc dose was reduced from 27.87Gy to 9.41Gy, respectively (p =0.001). 3D-CRT hybrid VMAT using DIBH technique significantly reduced the V5, V20 and D mean of the ipsilateral lung and D mean of the contralateral lung. The D5 of right breast was significantly reduced by 3D-CRT hybrid VMAT compared with VMAT using DIBH technique. Conclusion: The incorporation of DIBH into 3D-CRT hybrid VMAT technique provides the best benefits for the heart and the OAR with respect to the radiation dose-sparing effect without compromising the target conformity and homogeneity in the treatment planning.

Preliminary outcomes of accelerated partial breast irradiation by interstitial multicatheter brachytherapy with intraoperative free-hand catheter implantation in early breast cancer.

BACKGROUND: To evaluate the clinical feasibility of interstitial brachytherapy by intraoperative free-hand catheter implantation in the treatment of early breast cancer after breast-conserving surgery (BCS). METHODS: Between January 2018 and December 2019, 44 patients with early breast cancer after BCS who met the inclusion criteria ≥45 years old, invasive carcinoma ≤3 cm or ductal carcinoma in situ <2.5 cm, estrogen receptor positive, lymph node negative, surgical margin negative, no distant metastasis, and an ECOG performance score ≤1 were enrolled in this phase II single-arm study. The postoperative irradiation field includes the tumor bed plus 2-cm margin in all directions, except in the anterior-posterior direction. The total prescribed tumor dose was 3400 cGy delivered in 10 fractions twice daily at 6-hour intervals. The primary endpoints were acute side effects, late treatment-related toxicity, and cosmetic outcome. The secondary endpoints were local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS: The median follow-up time was 33.5 months (mean, 32.9 months; range, 20-43 months). The cosmetic results were good to very good in 92.3% of the questionnaire respondents. The acute toxicities were mild, and no acute grade 3-4 toxicity was noted. Wound infection was noted in two patients (4.5%). There was only one event of regional lymph node recurrence in one patient. The 3-year LRFS, DMFS, and OS were 100%, and RRFS was 94.7%. For two patients who had a positive lymph node based on their final pathology reports, postoperative irradiation, including whole breast and regional lymph nodes, was added. CONCLUSION: Accelerated partial breast irradiation using interstitial brachytherapy with the intraoperative free-hand catheter implantation technique provides an alternative method of postoperative radiotherapy for selected patients with early breast cancer after BCS with acceptable toxicities.

The clinical outcome of postoperative radiotherapy using hybrid planning technique in left breast cancer after breast-conserving surgery.

BACKGROUND: The purpose of this study is to observe the preliminary clinical outcome and acute toxicity of hybrid intensity modulated radiotherapy and volumetric modulated arc therapy planning technique with simultaneous integrated boost (SIB). METHODS: From November 2015 to December 2018, 149 female patients with left-side breast cancer who underwent adjuvant radiotherapy with hybrid IMRT and VMAT planning technique with SIB were reviewed retrospectively. The primary endpoint was acute toxicities and the secondary endpoints were local recurrence-free survival (LRFS), distant metastasis-freesurvival (DMFS), disease-free survival (DFS), and overall survival (OS). RESULTS: The median age was 52 years old and median follow-up was 43.4 months. Eighty-six percent of patients had acute grade 0 to grade1 dermatitis and 14% had grade 2 dermatitis. No acute radiation pneumonitis, esophagitis, or cardiovascular events were recorded during follow-up. The 3-year LRFS, DMFS, DFS, and OS rates were 95.1%, 95.1%, 90.3%, and 97.9%, respectively. The subgroup analysis revealed that patients with lymphovascular invasion had more local recurrence rate and worse DFS rate. Patients with advanced N stage had the trend of worse DMFS. CONCLUSION: In conclusion, the hybrid IMRT and VMAT technique is feasible, safe and has less acute radiation related toxicities in SIB postoperative radiotherapy for left-sided breast cancer.

Reasons for Altering Bladder Management and Satisfaction with Current Bladder Management in Chronic Spinal Cord Injury Patients.

Patients with spinal cord injury (SCI) often require bladder management. However, patients routinely change their bladder management for better satisfaction. The reasons for altering a bladder management method in SCI patients remain insufficiently understood. The purposes of this study are to assess current satisfaction with bladder management and the reasons for changing bladder management in SCI patients. A prospective cross-sectional survey with a convenience sampling method was used. The study was conducted from January 2018 to December 2019. The inclusion criteria included an age ≥18 years and a diagnosis of SCI more than one year previously. The questionnaires were self-administered and collected from eligible patients during a free clinic service. A total of 515 SCI participants were enrolled. Two hundred and eighty-three (55.0%) participants had experienced changing their bladder management. The most used method of current bladder management was self-voiding. About 84.7% of participants reported being satisfied with their current bladder management. Bladder management changes were most often made due to frequent urinary tract infections. Furthermore, the participants dissatisfied with their management had more urological complications. This study indicates that appropriate bladder management can improve the subjective satisfaction of patients. For long-term care, preventing urinary tract infections is a helpful strategy for patients' satisfaction with bladder management.

Adjuvant Chemotherapy for Pathological Node-Positive Disease in Squamous Cell Carcinoma of the Esophagus after Neoadjuvant Chemoradiotherapy Plus Surgery.

Purpose: The purpose of the present study is to determine the impact on survival using adjuvant chemotherapy on patients with locally advanced esophageal cancer. Materials and Methods: From 2007 to 2016, we enrolled 127 locally advanced esophageal squamous cell carcinoma patients treated with combined neoadjuvant chemoradiotherapy (nCRT) and surgery. For patients with the pathological residual primary disease (pT+) and/or residual node disease (pN+) after nCRT, adjuvant chemotherapy was also given after consideration of the toxicity of nCRT, patient performance, and/or comorbidity. The regimen of adjuvant chemotherapy was cisplatin 20 mg/m2/day and 5-fluorouracil 800 mg/m2/day on days 1 through 4 and 22 through 25. The primary endpoint was overall survival (OS). Results: From a total of 127 patients, 26 of them (20.5%) received adjuvant chemotherapy. In the multivariate analysis, pN+ diseases were independently associated with poor OS (hazard ratio (HR): 4.117, 95% confidence interval (CI): 1.366-12.404; p = 0.012). For those with pN+ diseases, their 5-year OS was 36.4% in the follow-up arm compared with 45.8% in the adjuvant chemotherapy arm (p = 0.094). Conclusions: Pathologic node-positive disease is associated with poor OS in locally advanced esophagus cancer patients after combined treatments with nCRT and surgery. Adjuvant chemotherapy appeared to have improved OS in pathologic node-positive diseases.

Good prediction of treatment responses to neoadjuvant chemoradiotherapy for esophageal cancer based on preoperative inflammatory status and tumor glucose metabolism.

To develop a tool for predicting pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (neoCRT) in patients with esophageal cancer by combining inflammatory status and tumor glucose metabolic activity. This study included 127 patients with locally advanced esophageal cancer who had received neoCRT followed by esophagectomy from 2007 to 2016. We collected their neutrophil-lymphocyte ratio (NLR) and standardized uptake value (SUV) obtained from fluorodeoxyglucose positron emission tomography (PET/CT) before and after neoCRT. Univariate and multivariate logistic regression analyses were performed to identify potential predictive factors for pCR. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of predictors were calculated. Between pCR and non-pCR groups, there were no statistically significant differences in patient characteristics, such as sex, age, site, and clinical T/N stage. Multivariate analyses identified four independent predictors for pCR, including pre-OP NLR < 5.4 [OR 11.179; 95% CI 8.385-13.495; p = 0.003], NLR change (ΔNLR) < 3 [OR 4.891; 95% CI 2.274-9.180; p = 0.005], changes in SUV (ΔSUV) > 7.2 [OR 3.033; 95% CI 1.354-6.791; p = 0.007], and SUV changes ratio (ΔSUV ratio) > 58% [OR 3.585; 95% CI 1.576-8.152; p = 0.002]. ΔNLR had the highest accuracy and NPV (84.3% and 90.3%, respectively). Combined factors of ΔNLR < 3 and ΔSUV ratio > 58% had the best PPV for pCR (84.8%). Inflammatory status (ΔNLR) and tumor glucose metabolic activity (ΔSUV ratio), when considered together, constitute a promising low-invasive tool with high efficacy for prediction of treatment response before surgery.

Dosimetric characteristics of accelerated partial breast irradiation by interstitial multicatheter brachytherapy with intraoperative free-hand implantation in the treatment of early breast cancer.

INTRODUCTION: The aim of this study is to evaluate the characteristics of the dosimetry and the skin dose of interstitial brachytherapy by the use of the free-hand implantation technique toward the treatment of early breast cancer. MATERIALS & METHODS: Seventeen patients diagnosed with early breast cancer were selected for the study. The implantation of the catheters for postoperative interstitial brachytherapy was performed using the free-hand technique. The total tumor dose to the tumor cavity plus 2 cm margin was 3400 cGy, twice daily for 10 fractions in 5 days. The dosage to the target and the organ at risk (OAR) were recorded for analysis. The skin dose of the patient and the phantom were measured with Gafchromic film (EBT3) and the results were compared with the skin dose calculated by the brachytherapy treatment planning system. RESULTS: The median conformal index is 94% (range 89%-99%), and the median homogeneity index is 71%. The median skin dose measured from the skin of the patients was 20.1% lower than the skin dose calculated from the treatment planning system and consistent with the phantom surface measurement experiment. There were no grade 3 or above acute toxicity recorded. CONCLUSIONS: Interstitial brachytherapy by the use of the free-hand implantation technique for early breast cancer is feasible and avoids the need for a second surgical intervention. The calculated skin dose was overestimated by at least 20%. The results of this study may help in building a modification model for the prediction of skin toxicity in any future study.

The clinical outcomes of elderly esophageal cancer patients who received definitive chemoradiotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) followed by an esophagectomy is the standard treatment for locally advanced esophageal cancer, but remains a great challenge for elderly patients. Therefore, we aim to evaluate the efficacy of definitive CRT in elderly patients with esophageal cancer. METHODS: From December 2007 to October 2017, 40 esophageal cancer patients aged ≥70 years receiving definitive CRT were retrospectively analyzed. All patients received cisplatin-based chemotherapy. Ten patients received standard doses of cisplatin 20 mg/m and fluorouracil (5-FU) 800 mg/m for 4 days, during the first and fifth weeks of radiotherapy. Eighteen patients received modified doses of cisplatin 16 to 18 mg/m and 5-FU 600 to 800 mg/m. Twelve patients received lower doses of cisplatin 10 to 12 mg/m and 5-FU 400 to 600 mg/m. The endpoints were overall survival (OS), tumor response rate, and treatment compliance. RESULTS: The 3-year OS rate was 28.8% The 3-year OS rates for patients receiving standard, modified, and lower doses were 12.5%, 53.8%, and 0.0%, respectively (p = 0.05). There were 87.5% of patients completing the scheduled radiotherapy dose, along with two cycles of concurrent chemotherapy. The response rate (clinical complete response and partial response rate) was 70.0%. Multivariate analysis revealed that no statistical difference was found in the OS among three groups of chemotherapy dosage. The treatment response was the only independent prognostic factor to OS (p < 0.001). CONCLUSION: Definitive CRT with dose modification is a feasible, safe, and reasonable treatment for elderly esophageal cancer patients. Achieving a better compliance to CRT via an optimal dose modification of chemotherapy may provide better clinical outcomes and would be the treatment goal for elderly esophageal cancer patients.

Adjuvant whole breast radiotherapy with simultaneous integrated boost to tumor bed with intensity modulated radiotherapy technique in elderly breast cancer patients.

BACKGROUND: Adjuvant whole breast radiotherapy is the standard of care for breast cancer patients after partial mastectomy. Intensity-modulated radiation therapy (IMRT) has been reported to reduce acute toxicities compared to conventional radiotherapy. IMRT with simultaneous integrated boost (SIB) technique can deliver higher doses to tumor bed and irradiate whole breast with a lower dose level to shorten overall treatment duration. This study presents the long-term results of adjuvant IMRT with SIB in elderly breast cancer patients who received partial mastectomy. METHODS: From January 2007 to January 2018, 93 elder breast cancer patients (≥65-year-old) who received IMRT with SIB technique after partial mastectomy were reviewed retrospectively. The axillary areas were managed with either sentinel lymph node biopsies or axillary lymph node dissection. The dose to whole breast was 50.4 Gy in 28 fractions in all patients and the dose to tumor bed was 61.6 to 66.4 Gy in 28 fractions. The primary end point is locoregional control. Secondary end points include: overall survival, breast cancer-specific survival, distant-metastases-free survival, disease-free survival, and acute and chronic toxicities. RESULTS: The median follow-up was 56.1 months. One patient had ipsilateral breast tumor recurrence, 3 patients had regional lymph node recurrence, and 9 patients had distant metastases. Death occurred in 5 patients, including 3 patients died of breast cancer progression. Five-year overall survival is 96.3% and 5-year locoregional recurrence-free survival is 96.4%. The 5-year breast cancer specific survival and 5-year distant metastases-free survival is 97.5% and 87.2%, respectively. Seven patients developed second primary cancer after RT. Eighty-one point seven percent patients had acute grade 1 dermatitis while 18.3% suffered from grade 2 dermatitis. The incidence of grade 1 pneumonitis and grade 1 stomatitis was 4.3% and 8.6%, respectively. CONCLUSIONS: Adjuvant IMRT with SIB technique is a safe and effective treatment strategy for elderly breast cancer patients after partial mastectomy.

Long-term outcome and symptom improvement in patients with interstitial cystitis/bladder pain syndrome with or without regular follow-up and treatment.

AIMS: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease, which is difficult to treat. Patients usually seek for new therapies and might not follow-up regularly. This study investigated long-term symptom changes in patients with IC/BPS, especially in those who were lost to follow-up. METHODS: We enrolled patients with IC/BPS with a history of >5 years and having comprehensive medical records, baseline IC symptom index and IC problem index, O'Leary-Sant symptom score, and visual analog scale (VAS). A telephone interview was conducted to assess current symptoms with the same questionnaires. A 5-point scale (from -1 to 3) was used to grade current treatment outcomes. RESULTS: A total of 198 patients with IC/BPS with a mean age of 57.4 ± 12.2 years were included. At a mean follow-up duration of 16.6 ± 9.75 years, 12% of the patients were free of symptoms and 47% exhibited symptom improvement of more than 50%. Totally, 47 (23.7%) patients were lost to follow-up for >5 years, and 151 (76.3%) had a regular follow-up. The patients with IC/BPS who were not regularly followed up had no Hunner's lesion, and had a higher bladder volume (P = .023), higher urine flow (P = .019), and fewer comorbidities (P = .014) than those who had a regular follow-up. The number of treatment modalities was significantly less in the patients who were lost to follow-up (P = .037). CONCLUSIONS: About half of the patients with IC/BPS exhibited symptom improvement with time, with or without regular follow-up and receiving a new treatment.

Monodehydroascorbate Reductase Plays a Role in the Tolerance of Chlamydomonas reinhardtii to Photooxidative Stress.

Monodehydroascorbate reductase (MDAR; EC 1.6.5.4) is one of the key enzymes in the conversion of oxidized ascorbate (AsA) back to reduced AsA in plants. This study investigated the role of MDAR in the tolerance of Chlamydomonas reinhardtii P.A. Dangeard to photooxidative stress by overexpression and downregulation of the CrMDAR1 gene. For overexpression of CrMDAR1 driven by a HSP70A:RBCS2 fusion promoter, the cells survived under very high-intensity light stress (VHL, 1,800 µmol�m-2�s-1), while the survival of CC-400 and vector only control (vector without insert) cells decreased for 1.5 h under VHL stress. VHL increased lipid peroxidation of CC-400 but did not alter lipid peroxidation in CrMDAR1 overexpression lines. Additionally, overexpression of CrMDAR1 showed an increase in viability, CrMDAR1 transcript abundance, enzyme activity and the AsA: dehydroascorbate (DHA) ratio. Next, MDAR was downregulated to examine the essential role of MDAR under high light condition (HL, 1,400 µmol�m-2�s-1). The CrMDAR1 knockdown amiRNA line exhibited a low MDAR transcript abundance and enzyme activity and the survival decreased under HL conditions. Additionally, HL illumination decreased CrMDAR1 transcript abundance, enzyme activity and AsA:DHA ratio of CrMDAR1-downregulation amiRNA lines. Methyl viologen (an O2�- generator), H2O2 and NaCl treatment could induce an increase in CrMDAR1 transcript level. It represents reactive oxygen species are one of the factor inducing CrMDAR1 gene expression. In conclusion, MDAR plays a role in the tolerance of Chlamydomonas cells to photooxidative stress.

Anxiety severity does not influence treatment outcomes in patients with interstitial cystitis/bladder pain syndrome.

AIMS: Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) typically experience anxiety mood status, which is closely connected with physical and psychological status and treatment outcome. This study aimed to evaluate the impact of anxiety severity on therapeutic results in IC/BPS patients. METHODS: We prospectively enrolled IC/BPS patients who had previously undergone any kind of treatment for their disease. The primary endpoint was a change in Beck Anxiety Inventory (BAI) scores at 3 months after treatment. Secondary endpoints included changes in the Global Response Assessment (GRA), O'Leary-Sant symptom score (OSS), and Numerical Rating Scale (NRS) at 3 months after treatment. Urodynamic studies were also compared with the clinical symptom scores. RESULTS: Overall, 85 IC/BPS patients (mean age, 53.1 ± 12.4 years) were included in the study. At 3 months, changes in the GRA were not significantly different among the different anxiety severity groups. At baseline, 55 (64.7%) patients had moderate or severe anxiety. We observed a significant positive correlation between the change in BAI and the change in OSS after treatment and a significantly negative correlation with GRA at 3 months. Moreover, improvements in OSS and NRS were associated with the change in GRA. Changes in IC symptoms, but not physiological outcomes, were associated with improved anxiety status after treatment. In addition, the change in BAI was significantly associated with age, baseline BAI, and changes in OSS and GRA after treatment. CONCLUSIONS: Baseline anxiety severity does not influence treatment outcomes of IC/BPS. Patients should receive active treatment regardless of their baseline anxiety status.

Definite intensity-modulated radiotherapy with concurrent chemotherapy more than 4 cycles improved survival for patients with locally-advanced or inoperable esophageal squamous cell carcinoma.

We investigated which prognostic factor could improve survival for esophageal cancer patients who received definite concurrent chemoradiation (CCRT). Eighty patients with age ≥18, Karnofsky Performance Scale (KPS) ≥ 60, and clinical stage T1-4N0-3M0 esophageal squamous cell carcinoma were enrolled from July 2004 to December 2015. They underwent definite intensity-modulated radiotherapy (IMRT) with or without simultaneous integrated boost to the primary tumor, and reception of concurrent chemotherapy ≥ 1 cycle. The primary endpoints were overall survival (OS), locoregional progression-free survival (LRPFS) and distant metastasis-free survival (DMFS). The median follow-up duration for alive patients was 21.5 months. The rates of 2-, 3- and 5-year OS/LRPFS/DMFS were 23.8%/53.5%/49.3%, 19.1%/44.6%/49.3%, and 13.0%/44.6%/43.9%, respectively. Only the non-clinical complete response (non-cCR) after CCRT was an independent poor prognostic factor in OS (HR 3.101, 95% CI 1.535-6.265, p = 0.0016). Radiation dose >50.4 Gy and chemotherapy ≥4 cycles significantly predicted better LRPFS (p = 0.0361 and 0.0163, respectively). Poorly differentiated tumor and stage III disease have poor DMFS (p = 0.0336 and 0.0411, respectively), and chemotherapy ≥ 4 cycles was a better predictor (p = 0.0004). In subgroup analysis, patients who received radiation dose ≤50.4 Gy with concurrent chemotherapy ≥4 cycles had the best survival outcome with 1-, 2-, 3- and 5-year survival rates of 73.7%, 39.4%, 31.5% and 17.5%, respectively. In conclusion, definite radiotherapy with concurrent chemotherapy ≥4 cycles improved the survival for patients with inoperable or locally-advanced esophageal squamous cell carcinoma.

The impact of pathological complete response after neoadjuvant chemoradiotherapy in locally advanced squamous cell carcinoma of esophagus.

BACKGROUND: The impact of pathological complete response after neoadjuvant chemoradiotherapy on survival of patients with squamous cell carcinoma of esophagus is still controversial. We retrospectively investigated the survival outcome in this group of patients. METHODS: Ninety-eight patients with locally advanced squamous cell carcinoma of esophagus, who received neoadjuvant chemoradiotherapy were included in this retrospective analysis. Treatment protocols were radiotherapy with standard dose 50.4 Gy/28 fr, and chemotherapy with cisplatin 20 mg/m2 and 5-FU 800 mg/m2 for 4 days given on week 1 and 5. After neoadjuvant chemoradiotherapy is completed, patients who were eligible for surgery received surgery within 4-6 weeks. Patients who were not suitable for surgery were shifted to definite chemoradiotherapy. The primary end points were overall survival and progression-free survival. RESULTS: Sixty-eight patients out of the ninety-eight patients received surgery after neoadjuvant chemoradiotherapy. There were 32 patients who achieved pathological complete response with a pCR rate of 47%. Thirty patients were shifted to definite concurrent chemoradiotherapy. The 2-year overall survival rate was 81.3% in the patients whose tumors showed a pCR and 58.3% in the patients with tumors that had a pathological partial response (p = 0.025). The 2-year overall survival in patients who received neoadjuvant chemoradiotherapy followed by surgery and definite chemoradiotherapy were 69.1% and 40.0%, respectively. There are 13 patients experienced grade 3-4 adverse event. CONCLUSION: Pathological complete response after neoadjuvant chemoradiotherapy is associated with a significant survival benefit in patients with locally advanced squamous cell carcinoma of esophagus. The toxicities related to neoadjuvant chemoradiotherapy were tolerable.

Phase II study of preoperative concurrent chemoradiotherapy with oxaliplatin for locally advanced esophageal cancer.

BACKGROUND: We investigated preoperative concurrent chemoradiotherapy (CCRT) with oxaliplatin for locally advanced, potentially operative esophageal cancer in this Phase II study. METHODS: Between October 2009 and October 2011, 35 consecutive patients with newly diagnosed esophageal cancer clinical stage T3-4, N0-1, M0 were enrolled into this study. One dose of chemotherapy with oxaliplatin (35 mg/m2) on Day 1 and Day 2, leucovorin (200 mg/m2) on Day 1, and 5-fluorouracil [5-FU; 2400 mg/m2 intravenously (i.v.) administered continuously for 48 hours] on Day 1 was administered 2 weeks before preoperative CCRT. During preoperative CCRT, radiation dose of 4500 cGy in 25 fractions was administered to the clinical target volume and 5000 cGy to 5040 cGy in 25 fractions was administered to the gross tumor volume; chemotherapy is administered concomitantly with oxaliplatin (45 mg/m2) on Day 1 of radiation therapy (R/T) every 14 days; 5-FU (400 mg/m2 i.v. bolus for 1 hour) for 5 days on Weeks 1 and 5 of R/T. Operation was performed 4-6 weeks after preoperative CCRT. Acute toxicity profile, overall survival rate, disease-free survival rate, distant metastasis failure-free survival rate, and local recurrence rate were evaluated. RESULTS: Four patients withdrew from the study. The total number of patients in this analysis was 31. The resection rate was 64.5%. The pathologic complete response rate was 15%. The overall median survival was 19.3 months. The 5-year overall survival rate was 37.8%. The 5-year disease-free survival rate was 31.1%. The 5-year distant metastasis failure-free survival rate was 40.7% (50.56% for patients with operation; 27.2% for patients without operation, p=0.0298). The acute toxicities were mild, and no Grade 3 or above hematologic toxicity was noted. There was only one patient with Grade 3 esophagus toxicity. Grade 3 lung toxicity occurred in only three patients. CONCLUSION: Preoperative chemoradiotherapy with oxaliplatin in the treatment of locally advanced, potentially resectable esophageal cancer is feasible and safe.

Persistent nasal carriers of Acinetobacter baumannii in long-term-care facilities.

BACKGROUND: Acinetobacter baumannii and Staphylococcus aureus have persisted as 2 major pathogens worldwide. AIM: We designed a prevalence study to investigate the prevalence of nasal carriage of S aureus and A baumannii in long-term-care facilities (LCTFs) and their collaborative community hospitals. In addition, we aimed to clarify persistent or nonpersistent carriage of the 2 organisms among residents of LTCFs. METHODS: We performed a prevalence study concerning nasal carriers of A baumannii and S aureus in 3 LTCFs and 1 collaborative community hospital. RESULTS: Seventy subjects were enrolled and clustered into 3 groups: the elderly sick group (n = 24), the elderly healthy group (n = 33), and the healthy health care worker group (n = 13). Nasal samples were collected, and the nuc and mecA genes of S aureus and the blaOXA gene of A baumannii were analyzed by polymerase chain reaction. Among the 3 groups, the rate of nasal carriage of S aureus was approximately 0%-15%. However, the rate for A baumannii was approximately 54%-92%. Notably, the persistent carrier rate of A baumannii in the elderly sick group was 83.3% (20 out of 24) despite a 12.5% (3 out of 24) rate of carbapenem-resistant A baumannii. CONCLUSIONS: We emphasized that the persistent nasal carriage of A baumannii in LTCFs could be another portal of exit to cause A baumannii infection in Taiwan.

Feasibility of intensity-modulated radiotherapy for esophageal cancer in definite chemoradiotherapy.

BACKGROUND: Esophageal cancer is a highly lethal malignancy, and its treatment has undergone a major evolution over the past 15 years. The objective of this study was to report our experience on the efficacy of definite chemoradiotherapy with the intensity-modulated radiotherapy (IMRT) technique in treating locally advanced esophageal cancer. METHODS: From September 2004 to November 2011, 39 patients with biopsy-proven esophageal cancer, clinical stage T1-4N0-3M0 according to the American Joint Committee on Cancer 7(th) edition were enrolled. In these enrolled cases, either the tumor was unresectable or the patients refused surgery. All patients received a total radiation dose of 40-56 Gy in 20-28 fractions using IMRT planning. Five to seven radiation beam angles were designed according to the specific shape of the clinical target volume (CTV) and were delivered by a linear accelerator with photons of 6-10 MV energy. The gross tumor volume, CTV, planning target volume, and the organs at risk were outlined, and the homogeneity index (HI) and the conformity index (CI) were calculated. The treatment-related toxicities were also reviewed. RESULTS: The mean follow-up time was 22.4 months (range, 2.0-91.0 months). The 2- and 3-year overall survival rates were 30% and 28%, respectively. The most common Grade 3/4 toxicity was hematologic toxicity (43.6%). The IMRT plans showed high-dose homogeneity to the target, with a calculated HI of 0.9. The calculated CI of 0.8 also showed high conformity treatment dose to target within an acceptable dose range. For the total lungs, the average mean dose was 1313.7 cGy. The V5 and V20 of the total lungs were 67.8% and 23.4%, respectively. For the heart, the average mean dose was 2319.2 cGy. The V30 and V35 of the heart were 30.2% and 21.5%, respectively. CONCLUSION: Concurrent chemoradiotherapy using the IMRT technique for treating locally advanced unresectable esophageal cancer is feasible, with better conformity of target volume as well as improved sparing of organs at risk.

Dosimetric comparison of hybrid volumetric-modulated arc therapy, volumetric-modulated arc therapy, and intensity-modulated radiation therapy for left-sided early breast cancer.

To compare the dosimetric performance of 3 different treatment techniques: hybrid volumetric-modulated arc therapy (hybrid-VMAT), pure-VMAT, and fixed-field intensity-modulated radiation therapy (F-IMRT) for whole-breast irradiation of left-sided early breast cancer. The hybrid-VMAT treatment technique and 2 other treatment techniques­pure-VMAT and F-IMRT­were compared retrospectively in 10 patients with left-sided early breast cancer. The treatment plans of these patients were replanned using the same contours based on the original computed tomography (CT) data sets. Dosimetric parameters were calculated to evaluate plan quality. Total monitor units (MUs) and delivery time were also recorded and evaluated. The hybrid-VMAT plan generated the best results in dose coverage of the target and the dose uniformity inside the target (p < 0.0001 for conformal index [CI]; p = 0.0002 for homogeneity index [HI] of planning target volume [PTV](50.4 Gy) and p < 0.0001 for HI of PTV(62 Gy)). Volumes of ipsilateral lung irradiated to doses of 20 Gy (V(20 Gy)) and 5 Gy (V(5 Gy)) by the hybrid-VMAT plan were significantly less than those of the F-IMRT and the pure-VMAT plans. The volume of ipsilateral lung irradiated to a dose of 5 Gy was significantly less using the hybrid-VMAT plan than that using the F-IMRT or the pure-VMAT plan. The total mean MUs for the hybrid-VMAT plan were significantly less than those for the F-IMRT or the pure-VMAT plan. The mean machine delivery time was 3.23 ± 0.29 minutes for the hybrid-VMAT plans, which is longer than that for the pure-VMAT plans but shorter than that for the F-IMRT plans. The hybrid-VMAT plan is feasible for whole-breast irradiation of left-sided early breast cancer.

To evaluate the treatment response of locally advanced esophageal cancer after preoperative chemoradiotherapy by FDG-PET/CT scan.

BACKGROUND: This study was designed to gauge the effectiveness of evaluation of tumor response and prognosis by positron emission tomography with 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) before and after preoperative chemoradiotherapy in patients with esophageal cancer. METHODS: Forty-nine patients from October 2008 to September 2012 with locally advanced stage esophageal carcinoma, clinical stage T2-4N0-3M0, who underwent preoperative chemoradiotherapy (pre-CRT) followed by esophagectomy were enrolled in our study. All patients underwent two FDG-PET scans to compare those results with the pathologic results. Metabolic response of the primary tumor by the percentage change of the SUVmax/1 hour (ΔSUV) before and after pre-CRT (ΔSUV was calculated as the difference between pre-CRT SUVmax/1 hour and post-CRT SUVmax/1 hour divided by pre-CRT SUVmax/1 hour at esophageal tumor) was evaluated for overall survival (OS), disease free survival (DFS), local recurrence rate, and distant failure free survival (DFFS). Prognostic factors such as age, different regimen of chemotherapy, pathologic stage, FDG-PET stage, endoscopic esophageal tumor length, and ΔSUV were analyzed. The number of highly suspect malignant lymph nodes was calculated by PET when SUVmax/1 hour ≥2.5 and by surgical removal. Sensitivity and specificity of regional lymph node detection by PET were also recorded. RESULTS: Upon univariate analysis, overall survival rate was related to ΔSUV >60% (p = 0.045), pathological N stage (p = 0.001), and endoscopic total length of esophageal tumor (p = 0.005). The result of FDG-PET scan after pre-CRT had high specificity (96.7%) but low sensitivity (45.8%) in predicting the residual malignant lymph node numbers. The positive and the negative prediction rates were 44% and 96%, respectively. The result of the FDG-PET after pre-CRT showed upstaged in 16 patients (32.6%), downstaged in nine patients (18.3%), and the same stage in 24 patients (48.9%) when compared with the pathologic stage [corrected]. CONCLUSION: The change of SUVmax can be a tool for evaluating tumor response after pre-CRT. There is also a trend of good prognosis in overall survival rate when ΔSUV value is >60%.