Postoperative radiotherapy timing, molecular subgroups and treatment outcomes of Thai pediatric patients with medulloblastoma.

INTRODUCTION: Medulloblastoma (MB) is the most common childhood malignant brain tumor worldwide. Recently, molecular classification was established and started to play a role in the management of MB; however, studies involving molecular defined MB in Southeast Asia have been limited. We aimed to describe, and correlate clinical characteristics and molecular subgroups with therapeutic outcomes of Thai pediatric patients with MB. MATERIALS AND METHODS: Pediatric MB patients treated at King Chulalongkorn Memorial Hospital in Thailand from 2006 to 2018 were recruited. Patients were classified by clinical characteristics into standard- and high-risk groups, which determined treatment regimen. Retrospectively, available tumor tissues were classified into 3 molecular subgroups using immunohistochemistry: 1) WNT, 2) SHH, and 3) non-WNT/non-SHH. The primary outcome was 5-year overall survival (OS). Risk factors associated with OS were analyzed using cox regression analysis. RESULTS: Fifty-three Thai pediatric patients with MB were enrolled. The median follow-up time was 60 months. The 5-year OS for all patients, and patients with standard-risk and high-risk were 74.2%, 76.3% and 71.4%, respectively. Tumor tissues of 24 patients were available, of which 23 could be molecularly classified. Two, one and 20 were in the WNT, SHH and non-WNT/non-SHH subtypes with 5-year OS of 100%, 100% and 78.9%, respectively. Using multivariate analysis, the interval of more than 8 weeks between surgery and radiotherapy was significantly correlated with a decrease in the 5-year OS. CONCLUSION: Interval between surgery and radiotherapy within 8 weeks was associated with good therapeutic outcomes among Thai pediatric patients with MB. Simplified molecular subtyping combined with clinical characteristics is practical in risk classification of patients with MB in institutes with limited resources.

Clinical Outcomes and Diagnostic Consistency of Serum and CSF Tumor Markers in Pediatric Intracranial Germ Cell Tumors in Thailand: A Multicenter Study.

The diagnostic and treatment outcomes of intracranial germ cell tumors (ICGCTs) among low and middle income countries are limited. A total of 63 ICGCTs patients with a median age of 11.6 years were studied. A 30 (47.6%) and 33 (52.4%) patients were classified as pure germinomas and nongerminomatous germ cell tumors (NGGCTs), respectively. The concordances between serum and cerebrospinal fluid (CSF) alpha-fetoprotein (84.3%) and beta-human chorionic gonadotropin (68.4%) were addressed. The 5-year overall survival (OS) and event-free survival (EFS) rates of pure germinomas versus NGGCTs were 83.9 versus 69.1% and 74.6 versus 57.7%, respectively. Patients undergoing radiation had higher 5-year OS and EFS than those without radiation treatment with P < .001. Chemotherapy combined with radiation is a cornerstone treatment to achieve outcomes. Adverse prognostic factors included age <8 years, surgery, and nonradiation treatment. Either serum or CSF tumor markers were adequately required as a diagnostic test among patients with ICGCTs.

KRAS Mutation in Pediatric Intracranial Germ Cell Tumors.

BACKGROUND: Intracranial germ cell tumors (IGCTs) are rare, highly curable neoplasms. KRAS is a gene in the KIT/RAS signaling pathway, and KRAS mutations have been reported in patients diagnosed with IGCTs. OBJECTIVES: To describe the clinicopathologic and molecular features of KRAS mutation and the treatment outcome of children diagnosed with IGCTs. METHODS: Patients diagnosed with IGCTs at the Department of Pediatrics, King Chulalongkorn Memorial Hospital from 2007 to 2016 were retrospectively reviewed. DNA was extracted from formalin-fixed, paraffin-embedded tissue and used for molecular study. Mutations in codons 12, 13, and 61 of the KRAS gene were detected using the cobas® KRAS mutation test and pyrosequencing. RESULTS: Eighteen patients were diagnosed with IGCTs (11 males and 7 females): nine with germinomas and nine with non-germinomatous GCTs (NGGCTs). The age range of the patients was 5-14 years (median 10.5 years). Elevated markers were revealed in approximately 25% of the patients. Four patients (two with germinomas and two with NGGCTs) had leptomeningeal involvement. All patients underwent tumor biopsy and received neoadjuvant chemotherapy. Radiotherapy was administered in 16 patients, and craniospinal radiation was administered only in patients with leptomeningeal metastasis. With a median follow-up of 26 months, overall survival was 88.9% in the patients with germinomas and 37% in the patients with NGGCTs. Mutation of the KRAS gene was detected using pyrosequencing in one patient. The mutation located at codon 61, with frequency 38.3% units, nucleotide substitution CAA > CTA, and amino acid substitution, was Q61L. The patient carrying the mutant gene was diagnosed with germinoma with cerebrospinal fluid metastasis and eventually died from treatment-related toxicity. CONCLUSION: Our study revealed the treatment outcomes of IGCTs in Thai children. The metastatic germinoma patient with KRAS codon 61 mutation had a poor outcome, supporting that Q61L has a clinical correlation with IGCTs.

Long-term results of hypofractionation with concomitant boost in patients with early breast cancer: A prospective study.

AIM: To report the long-term local control and survival of patients with early breast cancer who had hypofractionated whole breast irradiation with concomitant boost (Hypo-CB). METHODS AND MATERIALS: Between October 2009 and June 2010, 73 patients with early breast cancer (T1-3N0-1M0) who underwent breast conserving surgery were enrolled into the study. Thirty-six of these participants received 50 Gy of conventional irradiation in 25 fractions over 5 weeks to the whole breast with a sequential boost to the tumor bed with 10-16 Gy in 5-8 fractions (Conv-SEQ). The other 37 participants received a hypofractionated dose of 43.2 Gy in 16 fractions with an additional daily concomitant boost (CB) of 0.6 Gy over 3 weeks (Hypo-CB). RESULTS: At a median follow-up time of 123 months, ipsilateral local recurrence (ILR) was found in 3 participants, 1 of whom was in the hypofractionated group. All 3 ILR were true local recurrence (TR). There were no significant differences in the 10-year disease free survival (DFS) and 10-year overall survival rates (OS) between the conventional and hypofractionated groups (93.9% vs. 94.4%, p = 0.96 and 91.9% vs. 91.6%, p = 0.792, respectively). CONCLUSION: This study showed that the effectiveness, DFS and OS were comparable between hypofractionated whole breast irradiation with a CB and the conventional irradiation with a sequential boost.

A Phase Ib Study of Alpelisib or Buparlisib Combined with Tamoxifen Plus Goserelin in Premenopausal Women with HR-Positive HER2-Negative Advanced Breast Cancer.

PURPOSE: This study reports the MTD, recommended phase 2 dose (RP2D), and preliminary efficacy of alpelisib or buparlisib used in combination with tamoxifen plus goserelin in premenopausal patients with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). PATIENTS AND METHODS: This study enrolled premenopausal women with HR+, HER2- ABC. Patients received tamoxifen (20 mg once daily) and goserelin acetate (3.6 mg every 28 days) with either alpelisib (350 mg once daily; n = 16) or buparlisib (100 mg once daily; n = 13) in 28-day cycles until MTD was observed. RESULTS: The criteria for MTD were not met for both alpelisib and buparlisib. The RP2D of alpelisib and buparlisib in combination with tamoxifen and goserelin were 350 mg and 100 mg, respectively. Both combinations met protocol-specified criteria for tolerability. The most common grade 3/4 treatment-emergent adverse events (TEAE) were hypokalemia (12.5%), hyperglycemia (6.3%), and rash (6.3%) for alpelisib and alanine aminotransferase increase (30.8%), aspartate aminotransferase increase (23.1%), and anxiety (15.4%) for buparlisib. TEAEs led to treatment discontinuation in 18.8% and 53.8% of alpelisib- and buparlisib-treated patients, respectively. Progression-free survival was 25.2 months in the alpelisib group and 20.6 months in the buparlisib group. CONCLUSIONS: The RP2Ds of alpelisib and buparlisib were 350 mg and 100 mg, respectively. No unexpected safety findings were reported. Although an early-phase study, data suggest that alpelisib plus endocrine therapy may be a potentially efficacious treatment that warrants further evaluation for premenopausal patients with HR+, HER2- ABC.See related commentary by Clark et al., p. 371.

Flattening filter free stereotactic body radiation therapy for lung tumors: outcomes and predictive factors.

BACKGROUND: Stereotactic body radiation therapy (SBRT) using flattening filter free (FFF) has been commonly used, however, its outcomes and predictive factors in lung tumors are limiting. Thus, we aim to assess the clinical outcomes of this approach and identify factors associated with outcomes in patients with early stage non-small cell lung cancer (NSCLC) and oligometastatic/oligoprogressive lung tumor (OLT). METHODS: Patients who underwent lung SBRT with FFF were retrospectively reviewed. All patients were delivered using volumetric modulated arc therapy (VMAT) technique. The primary outcome was local control (LC). The secondary outcomes were overall survival (OS) and toxicities. We assessed the association between LC and various factors in OLT. RESULTS: From February 2014 to July 2019, ninety-four patients and 129 lesions with median follow-up time of 30 months were included in the analysis. Twenty-six patients with 26 lesions were early NSCLC, while 68 patients with 103 lesions were OLT, 41.7% of which were from colorectal cancers (CRC) and 18.5% were from primary lung cancers. Two-year LC was 88.9% and 85.7% for early NSCLC and OLT, respectively. Two-year OS was significantly higher for early NSCLC than OLT (83.3% vs. 68.7%, P=0.035). In the multivariate analysis for OLT, CRC origin (hazard ratio, HR 10.59, 95% CI: 2.29-48.95, P=0.003) and gross tumor volume (GTV) mean BED10 ≤147 Gy (HR 5.16, 95% CI: 1.13-23.59, P=0.034) were significantly associated with higher local failure (LF). Most of the acute grade 1-2 toxicities were radiation pneumonitis (26.5%). No grade 3-5 event was observed. CONCLUSIONS: This study confirmed the clinical efficacy and safety of lung SBRT using FFF-technique. Our findings support the role of using a high BED10 regimen to achieve good LC for OLT and the potential role for dose escalation for primary CRC.

Results of intraoperative radiotherapy given as a boost after breast conserving-surgery.

BACKGROUND: Whole breast irradiation after breast-conserving surgery (BCS) with an external beam boost of 10-16 Gy is currently the standard treatment in breast cancer. Various modalities have been used for tumor bed boost irradiation. This study aimed to evaluate the local recurrence rate, overall survival rate (OSR), toxicity and cosmetic outcome of intraoperative radiotherapy (IORT) as a boost followed by whole breast irradiation in patients who received BCS. METHODS: This is a retrospective study. Between December 2009 and March 2017, 81 patients who underwent BCS with IORT as a boost were enrolled in this study. For IORT, a single dose of 20 Gy was delivered using a 30-50 kV photon beam, intraoperatively. All patients received whole breast radiation therapy (WBRT) of 42.5-50 Gy over 4-5 weeks. The primary endpoint was a 3-year local recurrence rate. Secondary endpoints included the OSR, toxicity and cosmetic outcome at 6 months after radiation treatment. RESULTS: At a median follow-up of 43 months, ipsilateral local recurrence was observed in one of the 81 patients (1.2%) which occurred in the same quadrant of the breast index. The 3-year OSR was 89.8%. Treatment was well-tolerated with no grade 3-4 acute and late toxicity, and 87% of patients were recorded as excellent-good cosmesis. CONCLUSIONS: The use of BCS with IORT as a boost resulted in a low local recurrence rate and excellent cosmetic outcome in early breast cancer. Thus, IORT as a boost could be considered as an alternative to an external beam boost. Prospective studies are needed to confirm this data.

The effect of deep inspiration breath-hold technique on left anterior descending coronary artery and heart dose in left breast irradiation.

PURPOSE: To determine the effect of the deep inspiration breath-hold (DIBH) technique on left anterior descending coronary artery (LAD) region and heart dose in left breast cancer irradiation. MATERIALS AND METHODS: Twenty-five left breast cancer patients who previously received breast-conserving surgery underwent computed tomography (CT) simulation with both free-breathing (FB) and DIBH techniques and four radiation treatment plans. The plan comprised the following with both the FB and DIBH techniques: whole breast (WB), and WB with internal mammary lymph nodes (WB+IMNs). The prescription dose was 50 Gy in 25 fractions. The doses to the LAD region, heart and lungs were compared. Moreover, in-field maximum heart distance (maxHD) and breast volume were analyzed for correlations with the mean heart dose (MHD). RESULTS: In the WB plan with DIBH vs. FB techniques, the mean radiation doses to the LAD region, MHD, and the left lung V20 were 11.48 Gy vs. 19.84 Gy (p < 0.0001), 2.95 Gy vs. 5.38 Gy (p < 0.0001), and 19.72% vs. 22.73% (p = 0.0045), respectively. In the WB+IMNs plan, the corresponding values were 23.88 Gy vs. 31.98 Gy (p < 0.0001), 6.43 Gy vs. 10.24 Gy (p < 0.0001), and 29.31% vs. 32.1% (p = 0.0009), respectively. MHD correlated with maxHD (r = 0.925) and breast volume (r = 0.6). CONCLUSION: The use of the DIBH technique in left breast cancer irradiation effectively reduces the radiation doses to the LAD region, heart and lungs. MHD is associated with maxHD and breast size.

Management of intracranial germ cell tumors at the King Chulalongkorn Memorial Hospital.

OBJECTIVE: To study the outcome of less aggressive radiotherapy combined with surgery and chemotherapy to reduce radiation complication in the treatment of intracranial germ cell tumor (ICGCT) at the King Chulalongkorn Memorial Hospital. MATERIAL AND METHOD: A descriptive study was established by reviewing patients' records from the Division of Therapeutic Radiology and Oncology admitted between 2001 and 2008. Median follow-up time was 65 months. Patient characteristics, investigations, and treatment modalities were presented in proportion. Survival analysis was evaluated by Kaplan-Meier method. The results were compared with the previous study in done in 1990 to 2000. RESULTS: Forty-two records were reviewed and 71% were male. The median age was 16 years. Pineal region was the most common site in 55%. Interestingly, 12% had synchronous lesions at both pineal and suprasellar regions. Out of 41 patients who had histopathological confirmation, 71% were germinoma. Out of 37 patients who had MRI spine or CSF cytology, 43% had CNS dissemination. Less aggressive radiotherapy combined with surgery and chemotherapy was increasingly utilized; however five-year overall survival rate in all patients was 83%, comparable to 82% from the previous study. Survival rates of patients without CNS dissemination were 88% in the present study and 83% in the previous study. Survival rates adjusted for histopathology were 86% for germinoma and 76% for non-germinoma. CONCLUSION: Less aggressive radiotherapy combined with surgery and chemotherapy to reduce radiation complication is an effective treatment for ICGCT.

Phase II trial of capecitabine plus cisplatin as first-line therapy in patients with metastatic nasopharyngeal cancer.

BACKGROUND: Capecitabine is an oral fluoropyrimidine with single-agent activity in metastatic nasopharyngeal carcinoma (NPC). This multicenter phase II study was conducted to investigate the efficacy and safety of capecitabine plus cisplatin as a first-line treatment for metastatic NPC. METHODS: Patients with metastatic NPC received cisplatin 100 mg/m(2) day 1 plus capecitabine 1000 mg/m(2) twice daily on days 1 to 14 every 3 weeks for 6-8 cycles. The primary endpoint was overall response rate. RESULTS: Forty-four patients were enrolled; 39 patients were evaluable for efficacy. The overall response rate was 53.8% (95% confidence interval [CI], 37%-70%), including 1 complete response. Median time to tumor progression was 7.3 months (95% CI, 5.6-9.9 months) and median overall survival was 28.0 months (95% CI, 14.5 months-not reached). Common grade 3/4 adverse events were neutropenia (50%), vomiting (11%), thrombocytopenia (9%), and nausea (7%). CONCLUSIONS: Capecitabine plus cisplatin is an active first-line combination in metastatic NPC that requires a short hospital stay.

A two-year experience of implementing 3 dimensional radiation therapy and intensity-modulated radiation therapy for 925 patients in King Chulalongkorn Memorial Hospital.

BACKGROUND AND OBJECTIVE: Three dimensional conformal radiation therapy (3D CRT) and intensity-modulated radiation therapy (IMRT) have been implemented at Department of Therapeutic Radiation and Oncology, King Chulalongkorn Memorial Hospital (KCMH) since July 2005. This is the first study in Thailand to evaluate the pattern of care and utilization of 3D CRT and IMRT for treatment in each individual cancer. MATERIAL AND METHOD: Between July 2005 and July 2007, 925 newly diagnosed cancer patients underwent IMRT or 3D CRT at KCMH. The authors retrospectively reviewed the experience and utilization of 3D CRT and IMRT for each disease site and region. RESULTS: There were 471 males and 454 females. There were 332 patients (35.9%) treated with IMRT. Among the 332 IMRT patients, there were 100, 32 and 27 nasopharyngeal, lung and prostate cancers, respectively. On the contrary, 593 patients (64.1%) were treated with 3D CRT. Among these, breast, cervix and lung cancers were the most common diseases. Except for head and neck as well as genitourinary cancer 3D CRT was still the main technique used in more than 60% of the patients at KCMH. CONCLUSION: 3D CRT and IMRT have been successfully implemented at KCMH for 2 years. Three dimensional conformal radiation therapy was still the main technique used in more than 60% of the patients at KCMH. Prospective studies evaluating tumor control and treatment sequelae are expected.

Promoter hypermethylation of CCNA1, RARRES1, and HRASLS3 in nasopharyngeal carcinoma.

In search for putative tumor suppressor genes critical of nasopharyngeal carcinoma (NPC), we analyzed the available information from the expression profiling in conjunction with the comprehensive alleotyping published data relevant to this malignancy. Integration of this information suggested eight potential candidate tumor suppressor genes, CCNA1, HRASLS3, RARRES1, CLMN, EML1, TSC22, LOH11CR2A and MCC. However, to confirm the above observations, we chose to investigate if promoter hypermethylation of these candidate genes would be one of the mechanisms responsible for the de-regulation of gene expression in NPC in addition to the loss of genetic materials. In this study, we detected consistent hypermethylation of the 5' element of CCNA1, RARRES1, and HRASLS in NPC tissues with prevalence of 48%, 51%, and 17%, respectively. Moreover, we found a similar profile of promoter hypermethylation in primary cultured NPC cells but none in normal nasopharyngeal epithelium or leukocytes, which further substantiate our hypothesis. Our data indicate that CCNA1, RARRES1, and HRASLS3 may be the putative tumor suppressor genes in NPC.

Effect of Amifostine to prevent radiotherapy-induced acute and late toxicity in head and neck cancer patients who had normal or mild impaired salivary gland function.

BACKGROUND: Amifostine has a potential role for salivary gland protection in head and neck cancer patients who had radiotherapy. MATERIAL AND METHOD: Sixty-seven head and neck cancer patients were randomized to receive radiotherapy or radiotherapy plus Amifostine. The efficacy of the treatment was determined by a questionnaire evaluating dryness of mouth and the oral comfort, the RTOG/EORTC acute/late radiation morbidity scoring criteria, collection of the whole saliva and the 99mTc-pertecnetate scintigraphy of the salivary glands. RESULTS: Amifostine significantly reduced the mean questionnaire scores from 6.49 to 3.73, the incidence of grade > or = 2 mucositis from 75% to 36% and acute xerostomia from 82% to 39%. The salivary gland function returned to normal at a rate of 36.3% in the Amifostine group versus 9.1% in the control group. CONCLUSION: Amifostine is effective in reducing the incidence and severity of acute mucositis, acute and late xerostomia in head and neck cancer patients.

Intensity-modulated radiation therapy in head-and-neck cancer, first report in Thailand.

OBJECTIVE: This is the first report in Thailand to evaluate the efficacy of using intensity-modulated radiotherapy (IMRT) in the primary treatment of head-and-neck cancer. MATERIAL AND METHOD: From July 2005 to March 2006, eighteen patients with head and neck cancer were treated with IMRT, fourteen of which were nasopharyngeal cancer. The median age at diagnosis was 52 years (range 23-58 years). The treatment plan composed of two sequential plans for PTV-low risk (50Gy in 25 fractions) and PTV-high risk (20Gy in 10 fractions). Chemotherapy was given to 13 patients with locoregionally advanced disease (stage T3/T4 and N2/3) using cisplatin (n = 3) or carboplatin (n = 10) every 3 weeks during the course of radiation therapy. RESULTS: The median overall treatment time was 49 days (range, 43-57 days), and 77.8 percent of the patients completed 35 fractions within 50 days. The clinical complete response and partial response rates at 3 months after complete radiation were 71.4% and 28.6%, respectively. However at the median follow-up of 5.6 months, the complete response rate increased to 89%. Treatment break during RT range from 3 to 7 days, was observed in three patients. All of them received concurrent chemoradiation. No distant metastasis was noted. CONCLUSION: The authors' experience of using concurrent chemotherapy with IMRT for a cohort of patients with head and neck carcinoma showed a very high rate response rate at early follow-up. Long-term clinical outcome is expected.

Reducing radiation dose to pelvic small bowel in cervical cancer patients treated with Ir-192 intracavitary brachytherapy by using urinary bladder distension.

OBJECTIVES: Several techniques and devices have been used in an attempt to minimize radiation dose to gastrointestinal tract while giving pelvic radiation. We evaluated the effect of urinary bladder distension to displace pelvic small bowel out of intracavitary brachytherapy field to minimize radiation dose to small bowel in cervical cancer patients. MATERIAL AND METHOD: Eleven cervical cancer patients who received Ir-192 intracavitary brachytherapy with tandem and transverse ovoids were included in this study. Oral contrast material was used to visualize pelvic small bowel. Urinary bladder was distended by injection 125-200 ml. normal saline solution. Pelvic radiograph, anteroposterior and lateral view, was performed before and after bladder distention for brachytherapy treatment planning and comparing radiation dose at small bowel. RESULTS: The average maximum radiation dose at small bowel before and after bladder distension were 3123 cGy and 1998 cGy respectively. The summation of small bowel dose was reduced 54.17% (p = 0.002). CONCLUSION: Urinary bladder distension could effectively displace pelvic small bowel and reduce the radiation dose to small bowel from Ir-192 intracavitary brachytherapy in cervical cancer patients.

Phase III randomized trial comparing LDR and HDR brachytherapy in treatment of cervical carcinoma.

PURPOSE: Intracavitary brachytherapy plays an important role in the treatment of cervical carcinoma. Previous results have shown controversy between the effect of dose rate on tumor control and the occurrence of complications. We performed a prospective randomized clinical trial to compare the clinical outcomes between low-dose-rate (LDR) and high-dose-rate (HDR) intracavitary brachytherapy for treatment of invasive uterine cervical carcinoma. METHODS AND MATERIALS: A total of 237 patients with previously untreated invasive carcinoma of the uterine cervix treated at King Chulalongkorn Memorial Hospital were randomized between June 1995 and December 2001. Excluding ineligible, incomplete treatment, and incomplete data patients, 109 and 112 patients were in the LDR and HDR groups, respectively. All patients were treated with external beam radiotherapy and LDR or HDR intracavitary brachytherapy using the Chulalongkorn treatment schedule. RESULTS: The median follow-up for the LDR and HDR groups was 40.2 and 37.2 months, respectively. The actuarial 3-year overall and relapse-free survival rate for all patients was 69.6% and 70%, respectively. The 3-year overall survival rate in the LDR and HDR groups was 70.9% and 68.4% (p = 0.75) and the 3-year pelvic control rate was 89.1% and 86.4% (p = 0.51), respectively. The 3-year relapse-free survival rate in both groups was 69.9% (p = 0.35). Most recurrences were distant metastases, especially in Stage IIB and IIIB patients. Grade 3 and 4 complications were found in 2.8% and 7.1% of the LDR and HDR groups (p = 0.23). CONCLUSION: Comparable outcomes were demonstrated between LDR and HDR intracavitary brachytherapy. Concerning patient convenience, the lower number of medical personnel needed, and decreased radiation to health care workers, HDR intracavitary brachytherapy is an alternative to conventional LDR brachytherapy. The high number of distant failure suggests that other modalities such as systemic concurrent or adjuvant chemotherapy might lower this high recurrence, especially in Stage IIB and IIIB.

Pattern of local-regional recurrence in patient with early breast cancer after mastectomy: an analysis of 357 cases at King Chulalongkorn Memorial Hospital.

A retrospective review was performed on 357 patients with early stage I-IIIA operable breast cancer who were treated with mastectomy and referred to the clinic at the Division of Radiation Therapy, Department of Radiology, King Chulalongkorn Memorial Hospital between Jan 1991 and Dec 2001. Patients characteristics, treatment modalities and pattern of local and regional failure were evaluated. The median and mean age in the present study were 49 and 50.2 years, respectively. Stage I, II and IIIA were 10.9%, 79.6% and 9.5%, respectively. One hundred and ninety-seven patients (55.2%) received postoperative radiation therapy (RT). Adjuvant chemotherapy was given in 247 patients (69.2%) while 122 patients (34.2%) received adjuvant hormonal therapy. Sixty one patients (17.1%) received both adjuvant chemotherapy and hormonal therapy. However, 12.6% (45/357) did not receive any adjuvant treatment. Median follow up time was 42.6 months (range 6-136 months). Ipsilateral supraclavicular node and chest wall were the most common sites of local-regional recurrence. The chest wall recurrence rate was 10.4% (37/357), which was 16.9% (27/160) in the non postoperative radiation (No RT) group and 5.1% (10/197) in the postoperative radiation (RT) group. For ispilateral supraclavicular node, the recurrence rate was 10.6% (38/357), which was 15.6% (25/160) and 6.6% (13/197) for non RT and RT groups, respectively. The incidence of ipsilateral axilla, ipsilateral internal mammary node and ipsilateral infraclavicular node recurrence rate were 4.2%, 3.6% and 0.8%, respectively. Overall, chest wall and ipsilateral supraclavicular node were the most common sites of local-regional recurrence in early stage operable breast cancer who underwent mastectomy Postoperative adjuvant radiation therapy decreased the risk of local-regional recurrence.

Polymeric immunoglobulin receptor polymorphisms and risk of nasopharyngeal cancer.

BACKGROUND: Epstein-Barr virus (EBV) associated nasopharyngeal cancer (NPC) is an important squamous cell cancer endemic in Southeast Asia and the Far East and can be considered a multifactorial genetic disease. This research explores potential associations between nasopharyngeal epithelial EBV receptor and NPC susceptibility. To prove the hypothesis, we evaluated two candidate genes, complement receptor 2 (CR2) and polymeric immunoglobulin receptor (PIGR) by using 4 SNPs, CR2IVS2-848C-->T, PIGRIVS3-156G-->T, PIGR1093G-->A and PIGR1739C-->T, to genotype 175 cases and 317 controls, divided into Thai, Chinese and Thai-Chinese based on their respective ethnic origins. RESULTS: The results obtained indicated that PIGR is an NPC susceptibility gene. The risk association pertaining to each ethnic group was detected for homozygous PIGR1739C with a significant ethnic group adjusted OR (95%CI) of 2.71(1.72-4.23) and p < 0.00001. Haplotype of the two missense PIGR SNPs, 1093G-->A and 1739C-->T, and sequence analyses have confirmed the role of the nucleotide PIGR1739 and excluded possibility of an additional significant nonsynonymous NPC susceptibility SNP. CONCLUSIONS: We present genetic evidence leading to hypothesize a possibility of PIGR to function as the EBV nasopharyngeal epithelium receptor via IgA-EBV complex transcytosis failure. The PIGR1739C-->T is a missense mutation changing alanine to valine near endoproteolytic cleavage site. This variant could alter the efficiency of PIGR to release IgA-EBV complex and consequently increase the susceptibility of populations in endemic areas to develop NPC.

Estrogen and progesterone receptors status in Thai female breast cancer patients: an analysis of 399 cases at King Chulalongkorn Memorial Hospital.

A retrospective review was performed on 576 patients who have been diagnosed breast cancer and referred to Division of Radiation Therapy, Department of Radiology, King Chulalongkorn Memorial Hospital between January 1995-September 2001. There were three hundred ninety nine cases of invasive breast cancer that available for estrogen (ER) and/or progesterone (PR) receptor status. The mean and median age in our study were 49.6 year and 49.0 year respectively. About 60.9 per cent of the patients were pre and peri-menopause and 37.8 per cent were post-menopause. Most of the histological cell type were invasive ductal carcinoma which comprised of 92.7 per cent. Histologic grading were nearly equal for moderately and poorly differentiated grade: 43.66 per cent and 40.66 per cent. The results of our study showed 53.4 per cent of 399 patients had ER positive and 42.1 per cent of 380 patients had PR positive. The proportion of ER+PR+, ER+PR-, ER-PR+, and ER-PR- were 36.31 per cent, 15.53 per cent, 5.79 per cent and 42.37 per cent respectively. Older age and post-menopause women had higher ER+. While patients with increase tumor size, poorly differentiated grading, increase positivity of axillary lymph nodes and higher stage have more chance of ER negative and PR negative.