A phase II study of oxaliplatin with 5-FU/folinic acid and concomitant radiotherapy as a preoperative treatment in patients with locally advanced rectal cancer.

OBJECTIVE: To evaluate the activity and safety of adding oxaliplatin to a standard chemoradiotherapy schema, including 5-fluorouracil (5-FU)/folinic acid (FA), in locally-advanced rectal cancer (LARC). METHODS: Two cycles of oxaliplatin 130 mg/m(2) plus FA 20 mg/m(2) bolus for 5 days and 5-FU 350 mg/m(2) continuous infusion for 5 days were given during week 1 and 4 of pelvic radiotherapy 46 Gy. Patients with a T3/4 and/or node-positive rectal tumour were eligible. Surgery was performed 4-6 weeks after radiotherapy. The primary endpoint was to determine the rate of pathological response. Secondary endpoints were to assess the rate of clinical response and the safety profile. RESULTS: Between March 2005 and January 2009, a total of 35 patients were enrolled. The pathological down-staging rate was 79% with a pathological complete response rate of 17%. The overall clinical response rate (assessed by computed tomography or transrectal ultrasound) was 77%. Grade 3 diarrhoea and Grade 3 neutropaenia were reported in 14% and 11% of the patients, respectively. Eleven patients did not undergo surgery: four of them refused the operation, and seven patients were inoperable due to disease progression. In 24 patients who had surgery, a sphincter-preserving procedure could be performed in 29%. At the median follow-up time of 28.1 months, 25 patients (71%) survived with no evidence of disease. CONCLUSION: The promising results in terms of pathological response, and the associated good safety profile of a regimen of oxaliplatin plus 5-FU/FA with concomitant radiotherapy, suggest that the regimen could be used in LARC.

A phase II study of oxaliplatin with 5-FU/folinic acid and concomitant radiotherapy as a preoperative treatment in patients with locally advanced rectal cancer

Objective: To evaluate the activity and safety of adding oxaliplatin to a standard chemoradiotherapy schema, including 5-fluorouracil (5-FU)/folinic acid (FA), in locally-advanced rectal cancer (LARC). Methods: Two cycles of oxaliplatin 130 mg/m2 plus FA 20 mg/m2 bolus for 5 days and 5-FU 350 mg/m2 continuous infusion for 5 days were given during week 1 and 4 of pelvic radiotherapy 46 Gy. Patients with a T3/4 and/or node-positive rectal tumour were eligible. Surgery was performed 4–6 weeks after radiotherapy. The primary endpoint was to determine the rate of pathological response. Secondary endpoints were to assess the rate of clinical response and the safety profile. Results: Between March 2005 and January 2009, a total of 35 patients were enrolled. The pathological downstaging rate was 79% with a pathological complete response rate of 17%. The overall clinical response rate (assessed by computed tomography or transrectal ultrasound) was 77%. Grade 3 diarrhoea and Grade 3 neutropaenia were reported in 14% and 11% of the patients, respectively. Eleven patients did not undergo surgery: four of them refused the operation, and seven patients were inoperable due to disease progression. In 24 patients who had surgery, a sphincter-preserving procedure could be performed in 29%. At the median follow-up time of 28.1 months, 25 patients (71%) survived with no evidence of disease. Conclusion: The promising results in terms of pathological response, and the associated good safety profile of a regimen of oxaliplatin plus 5-FU/FA with concomitant radiotherapy, suggest that the regimen could be used in LARC.

Induction chemotherapy with paclitaxel, ifosfamide, and cisplatin followed by concurrent chemoradiotherapy for unresectable locally advanced head and neck cancer.

OBJECTIVE: Induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT) for locally advanced head and neck cancer has been studied in many clinical trials. This study was conducted to determine the response rate of IC with paclitaxel, ifosfamide, and cisplatin followed by CCRT with cisplatin for this group of patients, and the effect of the entire treatment on survival and time to disease progression. METHODS: Thirty patients with advanced and unresectable head and neck cancer were treated with 2 cycles of induction paclitaxel/ ifosfamide/ cisplatin. If the primary tumor had a complete or partial response, patients were treated with 2 more cycles of IC followed by radiotherapy 70 Gy plus 3 cycles of cisplatin. For those with less than partial response or disease progression were treated according to the discretion of the physicians. RESULTS: Ninety percent of patients had stage IV disease and 40% of them had primary tumor at maxillary sinus and nasal cavity. One patient (3%) achieved complete response (CR) and 18 patients had partial responses (PR) to IC. CCRT enhanced the response rate, resulting in a total of 3 CR (10%) and 16 PR (53%) to treatment. The median time to progression was 11.5 months. The median overall survival was 27 months. The most severe hematologic toxicity occurred during IC was grade3-4 neutropenia (40%). Grade 3-4 mucositis occurred in 68% of patients during CCRT. CONCLUSION: This novel combined-modality treatment program, is toxic but feasible, and can be administered for selected patients with advanced and unresectable head and neck cancer. © 2010 Biomedical Imaging and Intervention Journal. All rights reserved.

Can radiographic plain film be used to determine the depth of the tumour bed in the absence of surgical clips for breast boost planning.

PURPOSE: A number of studies have demonstrated the importance of using surgical clips to define the tumour bed in breast boost radiotherapy. In the absence of such clips, other techniques suggested to improve boost location have included CT and ultrasound (US). Determination of the depth of the tumour bed is important in the selection of electron energy. This study was conducted to prospectively compare the depth of the lumpectomy cavity as defined by ultrasound to radiographic plain film evaluation of the anterior border of the pectoralis muscle. MATERIALS AND METHODS: Forty-one breast-cancer patients treated at the Division of Therapeutic Radiology and Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University between December 2004 and December 2006 were prospectively identified as having no surgical clips within the lumpectomy cavity. All patients underwent both US evaluation of the depth of tumour bed (D1) and radiographic evaluation of the depth of the anterior border of the pectoralis muscle (D2). These depth dimensions (D1 and D2) were compared using a paired t-test. The correlation of both methods was analyzed by Pearson correlation test. RESULTS: Depth dimensions by US were shorter than the radiographic film method in 85% of patients. The absolute mean difference of the depth (radiographic films minus US) was 0.129 cm. A paired t-test demonstrated that the difference between these two methods to be not statistically significant (p= 0.27). The absolute difference of depth between the two methods ranged from 0 to 0.5 cm. A significant correlation was found between US and radiographic film measurements (p<0.01). CONCLUSION: Plane radiographic film evaluation of the anterior border of the pectoralis muscle can be used to define the depth of the tumour bed in patients who have no surgical clips. However, the plane radiographic film method determines only the depth, not the transverse and longitudinal dimensions of the tumour bed. Additional information from US is needed to delineate the target volume for the tumour bed boost. In the absence of surgical clips, the authors recommend integration of both methods in breast boost planning process.

Cancers in northern Thailand.

A retrospective study was undertaken to assess cancers in northern Thailand using the Chiang Mai Cancer registry and Maharaj Nakorn Chiang Mai Hospital records from January 2001 to December 2005. Maharaj Nakorn Chiang Mai Hospital is the university hospital for the Faculty of Medicine, Chiang Mai University. There were 4,108 new cancer cases being treated at the institution. The distribution of patients were (a) 32% from Chiang Mai, (b) 42% from nearby provinces of Lampoon, Phayao, and Chiang Rai, (c) 20.4% from other northern provinces, and (d) 1.2% from other parts of Thailand. Based on the data, the most common cancers by relative frequency are cancers of the lung, cervix, liver, breast, and non-Hodgkin's lymphoma. The current treatment options used to manage these most common cancers are described in this article.

Outcomes of abandoned radical hysterectomy in patients with stages IB-IIA cervical cancer found to have positive nodes during the operation.

The objective of this study was to evaluate the outcomes of stages IB-IIA cervical cancer patients whose radical hysterectomy (RH) was abandoned for positive pelvic nodes detected during the operation compared with those found to have positive nodes after the operation. Among 242 patients with planned RH and pelvic lymphadenectomy (RHPL) for stages IB-IIA cervical cancer, 23 (9.5%) had grossly positive nodes. RH was abandoned, and complete pelvic lymphadenectomy was performed. Of these 23 patients, 22 received adjuvant chemoradiation, and the remaining 1 received adjuvant radiation. Four patients with positive para-aortic nodes were additionally treated with extended-field irradiation. When compared with 35 patients whose positive nodes were detected after the operation, there were significant differences regarding number of positive nodes and number of patients receiving extended-field irradiation. Complications in both groups were not significantly different, but the 2-year disease-free survival was significantly lower in the abandoned RH group compared with that of the RHPL group (58.5% versus 93.5%, P= 0.01). In conclusion, the survival of stages IB-IIA cervical cancer patients whose RH was abandoned for grossly positive pelvic nodes was significantly worse than that of patients whose node metastasis was identified after the operation. This is because the abandoned RH group had worse prognostic factors.

Analysis of 587 cases of oral squamous cell carcinoma in northern Thailand with a focus on young people.

The increasing incidence of oral squamous cell carcinoma (SCC) especially among younger people has been observed in many parts of the world. The objective of this study was to delineate the profile of patients with oral SCC with an emphasis on younger people in northern Thailand between 1991-2000. The medical records of 587 (median age 65, male-to-female ratio 1:3:1) patients presenting oral SCC were reviewed, with details of demographic data, staging, histological grading, treatment modality and risk factor profile being collated in detail. Seventy-five patients (12.8%) were 45 years of age or below (median age, 39 years). Most patients regardless of age had stage IV disease (56.2%). The most common histological gradings were well or moderately differentiated SCC (79.4%). The most common site regardless was tongue (42.8%). Most patients (79.4%) received treatments with either radiotherapy alone or a combination of surgery and radiotherapy. 64.4% of patients (87.2%) did not have a familial history of cancer. Collectively this data indicates that oral SCC remains a constant problem to the northern Thai population. In addition, the occurrence of oral SCC in young people is relatively high. Therefore, it is recommended that prevention of oral SCC with early detection, early treatment intervention, and withdrawal from risk habits are important factors for improving the wellbeing of these people.

Phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer.

We conducted a phase II trial to investigate the efficacy of concurrent chemoradiation in patients with stage III non-small-cell lung cancer (NSCLC). Thirty patients with inoperable NSCLC were enrolled onto a multicenter phase II trial of concurrent chemoradiation therapy. Patients received six weekly cycles of paclitaxel 45 mg/m(2) over 1 h; carboplatin at (area under the curve) AUC 2; and radiation therapy of 60 Gy. Radiation was administered to the primary tumor and regional lymph nodes (40 Gy over 4 weeks) followed by a boost to the primary tumor (20 Gy in 2 weeks). After the initial phase of concurrent chemoradiation, patients received an additional four cycles of paclitaxel 175 mg/m(2) over 3 h and carboplatin at AUC 6 every 3 weeks. The overall objective response rate of 30 assessable patients was 76.7%. At the median follow-up time of 13.1 months, the median survival time was 14.5 months (95% CI, 10.59-18.48). The median progression-free survival was 10.5 months (95% CI, 7.72-13.28). The major toxicity was hematologic. The incidence of grade 3 esophagitis was 10%. In conclusion, this chemoradiation regimen is well tolerated and shows significant clinical results for locally advanced NSCLC. Locoregional failure rate remains an important issue with this newer chemotherapeutic regimen. A novel chemotherapy and radiation therapy is clearly needed.

Measurement of the dose components of fast and thermal neutrons and photons from a 0.1 mg 252Cf source in water for brachytherapy treatment planning.

The use of 252Cf in brachytherapy is expected to be more effective with the therapy of bulky tumors than the conventional therapy with photons. For treatment planning a code developed for calculation of gamma dose was used to generate the dose distributions of fast and 10B enhanced thermal neutrons and photons. Dose distributions of these components measured with ionization chambers and a GM counter were fitted to analytical functions as required by the modified treatment planning program. A comparison of these experimental results and the treatment planning output indicate good agreement. Therefore, the program may be used to optimize the brachytherapy procedure considering all three dose components. A realistic case of a patient being treated with conventional brachytherapy has been used to calculate the dose distribution that would be obtained by use of the 252Cf source.

High-dose-rate afterloading brachytherapy in carcinoma of the cervix: an experience of 1992 patients.

PURPOSE: To report the results of radiation therapy in carcinoma of the cervix treated by external irradiation and high-dose-rate (HDR) intracavitary brachytherapy. METHODS AND MATERIALS: This is a retrospective analysis of 2,063 patients with histologically proven carcinoma of the cervix treated by external irradiation and HDR intracavitary brachytherapy between March 1985-December 1991. The Kaplan-Meier method was used for survival and disease-free survival analysis. Late complications in the bowel and bladder were calculated actuarially. RESULTS: There were 71 patients who did not complete the course of irradiation so only 1992 patients were retrospectively analyzed for survival. There were 2 patients (0.1%) in Stage IA, 211 (10.2%) Stage IB, 225 (10.9%) in Stage IIA, 902 (43. 7%) in Stage IIB, 14 (0.7%) in Stage IIIA, 675 (32.7%) in Stage IIIB, 16 (0.8%) in Stage IVA, and 16 (0.8%) in Stage IVB. The median follow-up time was 96 months. The actuarial 5-year disease-free survival rate was 79.5%, 70.0%, 59.4%, 46.1%, 32.3%, 7.8%, and 23.1% for Stage IB, IIA, IIB, IIIA, IIIB, IVA, and IVB respectively. The actuarial 5-year disease-free survival rate for Stage IB(1) and IB(2) squamous cell carcinoma was 88.7% and 67.0%. The actuarial 5-year overall survival rate was 86.3%, 81.1%, 73.0%, 50.3%, 47.8%, 7.8%, and 30.8% for Stage IB, IIA, IIB, IIIA, IIIB, IVA, and IVB respectively. Pattern of failure revealed 20.8% local recurrence, 18. 7% distant metastases, and 4% in both. The late complication rate Grade 3 and 4 (RTOG) for bowel and bladder combined was 7.0% with 1. 9% Grade 4. CONCLUSION: HDR brachytherapy used in this series produced pelvic control and survival rates comparable to other LDR series.

Phase II study of concurrent chemoradiotherapy for inoperable (bulky) stage III (A/B) non-small cell lung cancer (NSCLC): a preliminary report.

We designed a phase II study to determine the feasibility and toxicity of concomitant radiotherapy and Paclitaxel/Carboplatin followed by adjuvant chemotherapy of the same regimen in patients with newly diagnosed inoperable stage III A/B non-small cell lung cancer. Patients were irradiated with a total dose of 66 Gy. Weekly courses of Paclitaxel 45 mg/m2 and Carboplatin AUC 2 were administered intravenously during the irradiation period. After completion of concurrent chemoradiotherapy, adjuvant chemotherapy with Paclitaxel 175 mg/m2 and Carboplatin AUC 6 intravenously every 3 weeks for 4 cycles were given. Since March 1998, 15 patients have been enrolled. All patients were assessable for efficacy and toxicity after concurrent chemoradiotherapy. Eleven patients were assessable for efficacy and toxicity after adjuvant chemotherapy. After concomitant chemoradiotherapy, complete response (CR) was documented in 2 of 15 (13%). Partial response (PR) was documented in 9 of 15 (60%). After completion of adjuvant chemotherapy in 11 patients, the overall response rate was 91 per cent. (18% CR, 73% PR). There were 8 per cent gr. 3-4 neutropenia which occurred during adjuvant chemotherapy. Concomitant Paclitaxel/Carboplatin and radiotherapy are promising modalities in the treatment of inoperable stage III A/B non-small cell lung cancer.

Preliminary report of the Asian-Oceanian Clinical Oncology Association randomized trial comparing cisplatin and epirubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Asian-Oceanian Clinical Oncology Association Nasopharynx Cancer Study Group.

BACKGROUND: The aim of this trial was to compare the outcome achieved with neoadjuvant chemotherapy followed by radiotherapy to that achieved with radiotherapy alone for patients with locoregionally advanced undifferentiated or poorly differentiated nasopharyngeal carcinoma (NPC) meeting one of the following criteria: Ho's T3 disease, Ho's N2-N3 disease, or lymph node size > or =3 cm. METHODS: Between September 1989 and August 1993, 334 patients were enrolled in the study, with equal numbers of patients randomized to the neoadjuvant chemotherapy arm (CT arm) and the radiotherapy arm (RT arm). Neoadjuvant chemotherapy consisting of 2-3 cycles of cisplatin (60 mg/m2 on Day 1) and epirubicin (110 mg/m2 on Day 1) followed by radiotherapy was given to the CT arm. For radiotherapy, a dose of 66-74 gray (Gy) (median, 71 Gy) was delivered to the primary tumor and 60-76 Gy (median, 66 Gy) to the neck. Two hundred eighty-six eligible patients completed the treatment and were evaluable for treatment response (134 in the CT arm, 152 in the RT arm). All patients were included in the survival analysis based on the intention to treat. The median follow-up was 30 months for the whole cohort and 41 months for the surviving patients. RESULTS: Analysis of the 334 patients based on the intention to treat showed no significant difference in relapse free survival (RFS) or overall survival (OS) between the 2 treatment arms (3-year RFS rate: 48% in the CT arm vs. 42% in the RT arm, P = 0.45; 3-year OS rate: 78% vs. 71%, P = 0.57). In an efficacy analysis based on only the 286 evaluable patients, a trend of improved RFS favoring the CT arm was observed (3-year RFS rate: 58% vs. 46%, P = 0.053), with again no significant difference in OS (3-year OS rate: 80% vs. 72%, P = 0.21). In the subgroup of 49 patients with bulky neck lymph nodes >6 cm, improved RFS (3-year RFS rate: 63% vs. 28%, P = 0.026) and OS (3-year OS rate: 73% vs. 37%, P = 0.057) were observed, favoring the CT arm. CONCLUSIONS: This multicenter randomized study did not demonstrate any benefit with the addition of cisplatin-epirubicin neoadjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma; therefore routine administration of neoadjuvant chemotherapy to this target group cannot be recommended. Although the overall incidence of recurrence was reduced with the addition of chemotherapy in the efficacy analysis, the overall survival was not affected. A more effective chemotherapy regimen, the selection of an appropriate target group, and the use of an alternative strategy for combining chemoradiotherapy should be explored in future trials.

Induction chemotherapy and irradiation in advanced carcinoma of the cervix.

The survival rate of patients with locally advanced cervical cancer has not changed during the past several years. The purpose of the study is to evaluate the efficacy of concomitant Mitomycin and 5-FU with irradiation. Six hundred seventy-three patients were randomized into four arms. Arm one RT alone, no maintenance chemotherapy Arm two RT alone, with maintenance chemotherapy Arm three RT concomitant chemo, no maintenance Arm four RT concomitant chemo, with maintenance Concomitant chemotherapy used Mitomycin C 10 mg/m2 day 1, 30 and oral 5-FU 300 mg/day day 1-14 and 42-56. Maintenance chemotherapy was oral using 5-FU 200 mg/day for 4 weeks with 2 weeks rest every 6 weeks for 3 courses. Six centers participated in the trial. The side effects were higher in concomitant chemotherapy arms, especially hematologic toxicity. Median follow-up time was 25 months (range 15 to 59 months). The disease-free survival data from life table analysis suggested a better disease-free survival in arms 3 and 4 (concomitant arms) and arm 2 (maintenance oral 5-FU arm) than in control (RT alone arm). The pattern of failure showed a greater difference in loco-regional recurrence in stage IIB than IIIB patients. This interim analysis shows a trend favoring the arm with concomitant chemotherapy.

Epirubicin and cisplatin in recurrent, metastatic or advanced carcinoma of the cervix.

The purpose of this study is to determine the efficacy of combination chemotherapy using Cisplatin and Epirubicin in carcinoma of the cervix. Fifty-six patients with local recurrent and/or metastatic carcinoma of the cervix have been treated using Cisplatin 60 mg/m2 and Epirubicin 90-100 mg/m2 every three weeks. The overall response rate was 67.9% (CR 14.3%, PR 53.6%). The response rate was higher in a previously non-treated metastatic area (PR+CR = 93.7%). Four out of fourteen patients in stage IVB had long-term survival ranging from 14 to 85 months. The toxicity was moderate. Leukocytopenia grade IV occurred in 20%. The combination is effective in carcinoma of the cervix, especially in previously non-treated patients.

Randomized trial of epirubicin and cisplatin chemotherapy followed by pelvic radiation in locally advanced cervical cancer. Cervical Cancer Study Group of the Asian Oceanian Clinical Oncology Association.

PURPOSE: Pelvic radiation is standard treatment for women with stage IIb to IVa cervical cancer, but treatment results are disappointing, particularly for women with bulky tumors. We investigated the role of primary chemotherapy followed by pelvic radiotherapy in a randomized trial. PATIENTS AND METHODS: Two hundred sixty patients with stage IIb and IVa cervical cancer received either standard pelvic radiotherapy or primary chemotherapy with cisplatin 60 mg/m2 and epirubicin 110 mg/m2 administered at 3-week intervals for three cycles, followed by pelvic radiotherapy. RESULTS: Ninety-nine patients have relapsed with a median follow-up duration of 1.3 years; in 62 patients, the first site of progressive disease was the pelvis. Patients who received primary chemotherapy had a significantly higher pelvic failure rate than those who received radiotherapy alone (P < .003). Seventy-six patients have died, and those who received primary chemotherapy had significantly inferior survival compared with those who received radiotherapy alone (P = .02). Tumor response following chemotherapy was observed in 63%. After radiotherapy, tumor response occurred in 72% of those who received combined modality treatment, compared with 92% of those who received radiotherapy alone. CONCLUSION: Primary chemotherapy with epirubicin and cisplatin, although resulting in tumor response in a significant proportion of patients, is accompanied by an inferior local control rate and survival compared with standard pelvic radiotherapy alone.

Carcinoma of the nasopharynx in Chiang Mai University Hospital: a review of 205 cases.

Carcinoma of the nasopharynx is one of the common head and neck cancers in Southeast Asia. We had studied 205 cases of nasopharyngeal cancer who attended the ENT clinic of the Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand from 1980-1984. The majority of the patients were found in stage IV. One hundred and five patients received a curative dose of radiation therapy. The observed actuarial 5 year survival was 34 per cent. There was a significant decrease in survival of patients with T4 disease. Differences in age, sex, histopathology and N-stage did not affect the survival. So far, the only specific treatment we can offer patients is radiation therapy, so an earlier diagnosis must be established in order to get better results of treatment.