• Radiation Oncology Journal
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• v.32 no.3
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• pp.147-155
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• 2014

Purpose: This study was conducted to observe the outcomes of postoperative radiotherapy (PORT) with or without concurrent chemotherapy in resected non-small cell lung cancer (NSCLC) in single institution. Materials and Methods: From 2002 to 2013, 78 patients diagnosed with NSCLC after curative resection were treated with radiotherapy alone (RT, n = 48) or concurrent chemoradiation (CCRT, n = 30). The indications of adjuvant radiation therapy were N2 node positive (n = 31), close or involved resection margin (n = 28), or gross residual disease due to incomplete resection (n = 19). The median radiation dose was 57.6 Gy (range, 29.9 to 66 Gy). Results: Median survival time was 33.7 months (range, 4.4 to 140.3 months). The 5-year overall survival (OS) rate was 49.5% (RT 46% vs. CCRT 55.2%; p = 0.731). The 3-year disease-free survival rate was 45.5% (RT 39.4% vs. CCRT 55.3%; p = 0.130). The 3-year local control rate was 68.1% (RT 64.4% vs. CCRT 77.7%; p = 0.165). The 3-year DMFS rate was 56.1% (RT 52.6% vs. CCRT 61.7%; p = 0.314). In multivariate analysis, age ${\geq}66$ years and pathologic stage III were significant poor prognostic factors for OS. Treatment failure occurred in 40 patients. Four patients had radiologically confirmed grade 3 radiation pneumonitis. Conclusion: In NSCLC, adjuvant RT or CCRT after curative surgery is a safe and feasible modality of treatment. OS gain was seen in patients less than 66 years. Postoperative CCRT showed a propensity of achieving better local control and improved disease-free survival compared to RT alone according to our data.

• Radiation Oncology Journal
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• v.37 no.2
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• pp.91-100
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• 2019

Purpose: Internal mammary lymph node (IMN) involvement is associated with poor prognosis in breast cancer. This study investigated the treatment outcomes of initial clinically IMN-positive breast cancer patients who received adjuvant radiotherapy (RT), including IMN irradiation, following primary breast surgery. Materials and Methods: We retrospectively reviewed data of 95 breast cancer patients with clinically detected IMNs at diagnosis treated with surgery and RT between June 2009 and December 2015. Patients received adjuvant RT to the whole breast/chest wall and regional lymph node (axillary, internal mammary, and supraclavicular) areas. Twelve patients received an additional boost to the IMN area. Results: The median follow-up was 43.2 months (range, 4.5 to 100.5 months). Among 77 patients who received neoadjuvant chemotherapy, 52 (67.5%) showed IMN normalization and 19 (24.6%) showed a partial response to IMN. There were 3 and 24 cases of IMN failure and any recurrence, respectively. The 5-year IMN failure-free survival, disease-free survival (DFS), and overall survival (OS) were 96%, 70%, and 84%, respectively. IMN failure-free survival was significantly affected by resection margin status (97.7% if negative, 87.5% for close or positive margins; p = 0.009). All three patients with IMN failure had initial IMN size ≥1 cm and did not receive IMN boost irradiation. The median age of the three patients was 31 years, and all had hormone receptor-negative tumors. Conclusion: RT provides excellent IMN control without the support of IMN surgery. Intensity-modulated radiotherapy, including IMN boost for breast cancer patients, is a safe and effective technique for regional lymph node irradiation.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.334-342
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• 2002

Purpose : The aim of this study was to determine if postoperative adjuvant chemotherapy (CT) alone and concurrent chemoradiation (CCRT), following radical surgery, improved the disease free survival (DFS) and overall survival (OS) in rectal cancer AJCC stage II and III patients. Materials and Methods : A total of 144 patients with AJCC stage II and III rectal cancer who had had radical surgery between 1989 and 1999 were included in the study. Of these patients, 72 had been treated with postoperative CT, and the other 72 with postoperative CCRT. The chemotherapy regimen consisted of oral UFT on a daily basis for $1\~12$ months (median 12 months) or 5-FU ($500\;mg/m^2$ for 5 days) intravenous (IV) chemotherapy with 4 week intervals for $1\~18$ cycles (median 6 cycles). Radiation of 4,500 cGy was delivered to the surgical bed and regional pelvic lymph nodes area, followed by $540\~1,440\;cGy$ (median 540 cGy) boost to the surgical bed. The follow-up period ranged from 20 to 150 months, with a median of 44 months. Results : The 5-year OS was $60.9\%\;and\;68.9\%$ (p=0.0915), and the 5-year DFS was $56.1\%\;and\;63.8\%$ (p=0.3510) for postoperative CT and postoperative CCRT, respectively. In the stage nm patients, the 5-year OS was $71.1\%\;and\;92.2\%$, and the 5-year DFS was $57.3\%\;and\;85.4\%$ for postoperative CT and CCRT, respectively. The OS was significantly improved (p=0.0379) but the DFS was not with postoperative CCRT compared to the postoperative CT (p=0.1482). In the stage III patients, the 5-year OS was $52.0\%\;and\;55.0\%$, and the 5-year DFS was $47.8\%\;and\;49.8\%$ for postoperative CT and postoperative CCRT. There were no statistically significant differences between postoperative CT and CCRT (p=0.4280 and p=0.7891) in OS and DFS. The locoregional relapses were $16.7\%\;and\;12.5\%$ for postoperative CT and CCRT, respectively. The distant relapses were $25.0\%\;and\;26.4\%$ for postoperative CT and CCRT, respectively. Conclusion : These results showed that postoperative CCRT compared with CT alone improved OS in stage II patients. Although there was no statistical significance, the addition of postoperative RT to CT reduced locoregional relapses compared to CT alone.

• Radiation Oncology Journal
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• v.22 no.1
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• pp.17-24
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• 2004

Purpose: To evaluate the treatment outcomes after postmastectomy radiotherapy (PMRT) and chemotherapy in patients with breast cancer. Materials and Methods: The PMRT were retrospectively analyzed in 83 patients with stage II-III female breast cancer treated between 1989 and 1995. The median age was 46 years (range, 23-77): Seventy-seven patients had modified radical mastectomies, 5 radical mastectomies and 1 simple mastectomy. Three patients ($4\%$) had pathologically negative axillae, and the remaining 80 ($96\%$) had positive axillae. Eleven, 23, 44 and 5 patients had pathological stages IIA, IIB, IIIA, and IIIB, retrospectively. Eighty ($96\%$) patients were treated with hockey-stick fields. The median dose of PMRT was 50.4 ey, in 1.8 Gy fractions. Adjuvant systemic chemotherapy was given to 74 patients ($89\%$). CMF-based or doxorubicin-containing regimens were given to 54 patients ($55\%$). The median follow-up time was 82 months (range, 8-171) after the mastectomy. Results: The 5 and 10-year overall survival rates for all patients were 65 and $49\%$, respectively. The univariate and multivariate analyses of the factors affecting the overall survival revealed the stage to be the most significant prognostic factor (p=0.002), followed by the combination of chemotherapy. Thirteen patients $16\%$ developed a LRF, at an interval of 4-84 months after radiotherapy, with a median of 20 months. The only significant prognostic factor affecting LRF was the combination of chemotherapy, in both the univariate and multivariate analyses. With respect to the sequence of chemoradiation, the sequence had no saatistical significance (p=0.90). According to the time interval from mastectomy to the onset of radiotherapy, the LRFR of the patients group treated by RT within or after 6 month postmastectomy 6 months were 14 vs. $27\%$ respectively (p=0.24). One third of the pa41en1s (26/83) developed distant metastasis, in 2-92 months, after radiotherapy, with a median of 21 months. The most commonly involved site was bone in 13 cases. The pathological staging was the only significant prognostic factor in both the univariate and multivariate analyses that affected distant failure. Radiological finding of radiation pneumonitis on a simple chest x-ray was shown in $20\%$ (17/83), with a time interval ranging from 2 to 7 months post-radiotherapy, with a median of 3 months. The stable lung fibrosis settled in 11 patients ($65\%$). Conclusion: It was concluded through this analysis that the combination of PMRT with in chemotherapy resulted in better overall survival and local control than PMRT alone in patients needing PMRT.

• Journal of Life Science
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• v.24 no.10
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• pp.1137-1143
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• 2014

Doxorubicin is a general chemotherapy drug widely used for a number of cancers. However, the correlation between endogenous nitric oxide ($NO^{\bullet}$) levels and chemoresistance to doxorubicin remains unclear. In this study, we investigated the effect of endogenous $NO^{\bullet}$ on the anticancer activity of doxorubicin in human colon cancer cell lines HCT116 and HT29 with different p53 status. The cells were treated with either doxorubicin alone or in combination with the $NO^{\bullet}$ synthase (NOS) inhibitor $N^G$-monomethyl-L-arginine (NMA). Doxorubicin differentially inhibited the growth of both the HCT116 (p53-WT) and HT29 (p53-MUT) cells, which was mitigated by cotreatment with NMA. Further studies revealed that inhibition of endogenous $NO^{\bullet}$ mitigated doxorubicin-induced apoptosis in the HCT116 and HT29 cells, as evidenced by apoptotic DNA fragmentation and the sub-G1 peak of apoptotic markers. Apoptosis was delayed in the HT29 cells, and its magnitude was greatly reduced, underscoring the importance of the modulation of p53 in the response. RT-PCR analysis revealed that doxorubicin down-regulated levels of inhibitors of the apoptosis family (cellular IAP-1 and-2). Collectively, these data show that induction of apoptosis by doxorubicin in human colon cancer cells is possibly related to modulation of endogenous $NO^{\bullet}$, the expression of the IAP family of genes, and the status of p53. The underlying mechanisms may represent potential targets for adjuvant strategies to improve the efficacy of chemotherapy for colon cancer.

• The Journal of the Korean bone and joint tumor society
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• v.1 no.1
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• pp.84-90
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• 1995

To evaluate the role of radiation and chemotherapy after limb-saving operation in the management of soft tissue sarcoma, the authors analysed retrospectively 33 patients treated in department of Orthoaepdic Surgery and Radiation Therapy, Catholic University Medical College, in terms of survival rate, local recurrence rate and prognostic factors. There were 16 males and 17 females. The age distribution ranged from 16 to 81 years with mean age of 48. The follow-up period ranged from 2 to 10 years with average of 5.5 years. The histologic diagnoses were 9 liposarcoma(27.2%), 8 malignant fibrohistiocytoma(24.2%), 7 unclassifiable(21.2%), 3 rhabdomyosarcoma(9.1%), 2 malignant schwannoma, 2 synovral sarcoma, and 2 fibrosarcoma(6.1%) in orders. While marginal and intralesional margins were gained in 24 patients(72.7%), wide and radical margins were obtained only in 9 patients(27.3%). On postoperative 3 weeks, local irradiation of 5000-7000 cGy was delivered to all patients by shrinking field technique for 5-8 weeks. Of 33 patients, 16(45.5%) patients were received adjuvant chemotherapy in combination of adriamycin, cyclophosphamide & vicristine, or VP16 & ifosfamide based on histologic type and obtained surgical margin. The survival rates by direct method at 2 years and 5 years were 58% and 37% respectively. Local recurrences occured in 15 patients(45.5%) at average 16 months after operation. Survival rates at 2 years and 5 years were 37% and 22% in case of intralesional and manginal excision, 75% and 47% in case of wide and radical excision respectively with statistical significance(p<0.05). They were 25% and 17% in the presence of local recurrence, 67% and 42% in the absence of local recurrence respectively with statistical significance(p<0.05). Even though there was no statistical correlation between survival rate and tumor size(p>0.05), the authors considered tumor size as a significant prognostic factors as well as surgical margin and the presence of local recurrence.

• Journal of Korean Neurosurgical Society
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• v.30 no.5
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• pp.575-580
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• 2001

Purpose : In general, pineal region tumors are managed by using microsurgical approach or stereoctactic biopsy. However, in selected cases endoscopic approach to pineal lesions might prove to be as effective as microsurgery and less invasive. We report an alternative surgical strategy for managing certain patients with pineal neoplasms that allows treatment of the symptomatic hydrocephalus as well as tumor biopsy under direct vision in the same sitting. Materials and Methods : Twenty-two patients with pineal region tumors with associated hydrocephalus were treated in one session by endoscopic third ventriculostomy and endoscopic tumor biopsy at our institution from October 1996 to January 2000. All patients were retrospectively evaluated. Results : There was no operative mortality. There was one cause of significant bleeding during biopsy, but was controlled endoscopically, and the patient recovered completely without neurologic deficit resulting from intra-operative bleeding. The symptoms related to increased intracranial pressure(ICP) have resolved in all patients, and the need for a shunt is completely eliminated. Histological diagnosis was achieved in 21 of the 22 patients by this procedure. A biopsy was not obtained in one patient. Although this pineal region tumor was seen endoscopically, this could not be biopsied because of technical difficulties in working around an enlarged massa intermedia. The lesions included fourteen germinomas, three mixed germ cell tumors, and one each of the followings: pineocytoma, pineoblastoma, pineocytoma/pineoblastoma(intermediate type), meningioma, and low grade glioma. Five of the 22 patients subsequently underwent formal microsurgical tumor removal. Additional chemotherapy or radiotherapy could then be initiated according to the histological diagnosis. Conclusion : We consider that endoscopy affords a minimally invasive way of reaching three objectives by one-step surgery in the management of pineal region tumors with associated hydrocephalus : 1) cerebrospinal fluid(CSF) sample for analysis of tumour markers and cytology, 2) treatment of hydrocephalus by third ventriculostomy, and 3) several biopsy specimens can be obtained identifying tumors which will require further open surgery or adjuvant radiation and/or chemotherapy. However, complications and morbidities should be emphasized so as to be avoided with further technical experience.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3897-3901
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• 2016

Background: Breast cancer is by far the most frequent cancer of women (23% of all cancers), ranking second overall when both sexes are considered together. Since there has been change in clinico-pathological factors and treatment profiles for breast cancer patients over the years, the present study to evaluate the change trends in India. Materials and Methods: A detailed analysis was carried out with respect to age, menopausal status, family history, disease stage, surgery performed, histopathology, hormone receptor status, and use of chemotherapy or hormonal therapy. Change in various clinico-pathological factors and treatments of breast cancer cases was recorded and analysed. Results: Mean age at presentation was found to be earlier in 2005-2006 compared with 1997-98 (p value: 0.046). More premenopausal women were diagnosed with breast cancer in 2005-2006 when this was compared with initial years of assessment (p value ${\leq}0.001$). When change in the receptor status was evaluated, we observed that there was a decrease in cases of ER and PR receptor positivity which was significant (p value: 0.007). Over the period of time, more f patients were not offered surgery initially in view of advanced disease when the two time periods were compared (p value: ${\leq}0.001$). There was a significant increase in patients who were initially offered neo-adjuvant chemotherapy in view of advanced disease at presentation (p value: ${\leq}0.001$). There was increasing number of patients who received palliative treatment for symptoms in 2005-2006 when compared to patients treated in 1997-98((p value: ${\leq}0.001$). Conclusions: Changes in mean age at presentation, premenopausal status, and stage at presentation have occurred over the years. More aggressive patterns of disease have become more common with early age at presentation and aggressive biological behaviour with receptor negative tumours.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5989-5993
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• 2013

Background: Radiation therapy is the mainstay of treatment for nasopharyngeal carcinoma. Importance of tumor coverage and challenges posed by its unique and critical location are well evident. Therefore we aimed to evaluate our radiation treatment plan through dose volume histograms (DVHs) to find planning target volume (PTV) dose coverage and factors affecting it. Materials and Methods: This retrospective study covered 45 histologically proven nasopharyngeal cancer patients who were treated with definitive 3D-CRT and chemotherapy between Feb 2006 to March 2013 at the Department of Oncology, Section Radiation Oncology, Aga Khan University Hospital, Karachi, Pakistan. DVH was evaluated to find numbers of shrinking field (phases), PTV volume in different phases and its coverage by the 95% isodose lines, along with influencing factors. Results: There were 36 males (80%) and 9 females (20%) in the age range of 12-84 years. Stage IVA (46.7%) was the most common stage followed by stage III (31.1). Eighty six point six-percent received induction, 95.5% received concurrent and 22.2% received adjuvant chemotherapy. The prescribed median radiation dose was 70Gy to primary, 60Gy to clinically positive neck nodes and 50Gy to clinically negative neck regions. Mean dose to spinal cord was 44.2Gy and to optic chiasma was 52Gy. Thirty seven point eight-percent patients completed their treatment in three phases while 62.2% required four to five phases. Mean volume for PTV3 was $247.8cm^3$ (50-644.3), PTV4 $173.8cm^3$ (26.5-345.1) and PTV5 $119.6cm^3$ (18.9-246.1) and PTV volume coverage by 95% isodose lines were 74.4%, 85.7% and 100% respectively. Advanced T stage, intracranial extension and tumor volume > $200cm^3$ were found to be important factors associated with decreased PTV coverage by 95% isodose line. Conclusions: 3D CRT results in adequate PTV dose coverage by 95% isodose line. However advanced T stage, intracranial extension and large target volume require more advanced techniques like IMRT for appropriate PTV coverage.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4567-4570
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• 2013

Background: Nasopharyngeal carcinoma (NPC) is the commonest radiocurable cancer in Malaysia. This study aimed to determine the treatment outcomes and late effects of radiotherapy for NPC patients treated in University Malaya Medical Centre (UMMC). Materials and Methods: All newly diagnosed patients with NPC referred for treatment to the Oncology unit at UMMC from 2004-2008 were retrospectively analyzed. Treatment outcomes were 5 years overall survival (OS), disease free survival (DFS), cause-specific survival (CSS), locoregional control (LRC) and radiotherapy-related late effects. The Kaplan-Meier method was used for survival analysis and differences in survival according to AJCC stage was compared using the log-rank test. Results: A total of 176 patients with newly diagnosed NPC were treated in UMMC during this period. Late presentation was common, with 33.5% presenting with T3-4 disease, 84.7% with N1-3 disease and 75.6% with AJCC stage 3-4 disease. Radical RT was given to 162 patients with 22.7% having RT alone and 69.3% having CCRT. The stipulated OTT was 7 weeks and 72.2% managed to complete their RT within this time period. Neoadjuvant chemotherapy was given to 14.8% while adjuvant chemotherapy was administered to 16.5%. The 5 years OS was 51.6% with a median follow up of 58 months. The 5 years OS according to stage were 81.8% for stage I, 77.9% for stage II, 47.4% for stage III and 25.9% for stage IV. The 5 years overall CSS, DFS and LRC were 54.4%, 48.4% and 70.6%, respectively. RT related late effects were documented in 80.2%. The commonest was xerostomia (66.7%). Other documented late effects were hearing deficit (17.3%), visual deficit (3.1%), neck stiffness (3.1%), dysphagia (3.4%), cranial nerve palsy (2.5%), pneumonitis (0.6%) and hypothyroidism (1.2%). Conclusions: The 5 years OS and LRC in this study are low compared to the latest studies especially those utilizing IMRT. Implementation of IMRT for NPC treatment should be strongly encouraged.