Ivan Weng Keong Tham

Treatment of Nasopharyngeal Carcinoma using Intensity Modulated Radiotherapy - The National Cancer Centre, Singapore Experience

PURPOSEnThe aim of this study was to determine the efficacy and acute toxicity of our early experience with treating nasopharyngeal carcinoma (NPC) patients with intensity-modulated radiotherapy (IMRT).nnnMETHODS AND MATERIALSnA review was conducted on case records of 195 patients with histologically proven, nonmetastatic NPC treated with IMRT between 2002 and 2005. MRI of the head and neck was fused with CT simulation images. All plans had target volumes at three dose levels, with a prescribed dose of 70 Gy to the gross disease, in 2.0-2.12 Gy/fraction over 33-35 fractions. Cisplatin-based chemotherapy was offered to Stage III/IV patients.nnnRESULTSnMedian patient age was 52 years, and 69% were male. Median follow-up was 36.5 months. One hundred and twenty-three patients had Stage III/IV disease (63%); 50 (26%) had T4 disease. One hundred and eighty-eight (96%) had complete response; 7 (4%) had partial response. Of the complete responders, 10 (5.3%) had local recurrence, giving a 3-year local recurrence-free survival estimate of 93.1% and a 3-year disease-free survival of 82.1%. Fifty-one patients (26%) had at least one Grade 3 toxicity.nnnCONCLUSIONSnResults from our series are comparable to those reported by other centers. Acute toxicity is common. Local failure or persistent disease, especially in patients with bulky T4 disease, are issues that must be addressed in future trials.

Late toxicities after conventional radiation therapy alone for nasopharyngeal carcinoma.

BACKGROUND AND PURPOSEnWe sought to evaluate the nature and frequency of late toxicities in a cohort of nasopharyngeal cancer (NPC) patients treated with conventional radiotherapy alone.nnnMETHODS AND MATERIALSnSeven-hundred and ninety-six consecutive NPC patients treated using conventional radiotherapy at a single center from 1992 to 1995 were retrospectively analyzed. Patients with histology proven, completely staged, Stage I-IVB World Health Organization Type I-III NPC and completed radical radiotherapy were included. Patients with incomplete staging investigations, distant metastases at diagnosis, previous treatment, and incomplete radiotherapy were excluded. Radiotherapy-related complications were categorized using the RTOG Late Radiation Morbidity Scoring Criteria.nnnRESULTSnMedian follow-up was 7.2 years. The 5-year overall survival and disease free survival were 69% and 56%, respectively, and the corresponding 10-year rates were 52% and 44%. Among 771 patients with at least 3 months of follow-up post treatment, 565 (73%) developed RT-related complications. Diagnosed neurological complications were cranial nerve palsies (n=70; 9%), temporal lobe necrosis (n=37; 5%), Lhermittes syndrome (n=7; 1%), and brachial plexopathy (n=2; 0.3%). Non-neurological complications included xerostomia (n=353; 46%), neck fibrosis (n=169; 22%), hypo-pituitarism (n=48; 6%), hearing loss (n=120; 16%), dysphagia (n=116; 15%), otorrhea (n=101; 13%), tinnitus (n=94; 12%), permanent tube feeding (n=61; 8%), trismus (n=45; 6%), second malignancies within treatment field (n=17; 2%), and osteo-radionecrosis (n=13; 2%).nnnCONCLUSIONSnWhile radiotherapy is curative in NPC, many patients suffer significant late treatment morbidities with conventional radiotherapy techniques.

Intensity-Modulated Radiation Therapy Without Concurrent Chemotherapy for Stage IIB Nasopharyngeal Cancer

Objectives:To evaluate the treatment outcome of patients with stage IIB nasopharyngeal carcinoma (NPC) after definitive intensity-modulated radiotherapy (IMRT) without concurrent chemotherapy. Methods:Between August 2003 and December 2006, 107 patients with T1N1M0 (8%), T2N0M0 (13%), or T2N1M0 (79%) NPC were definitively treated with IMRT. Sixty-one received IMRT only, and 46 patients had various strategies of systemic treatment, consisting of abbreviated neoadjuvant (38 patients), concurrent (8 patients), or adjuvant (16 patients) chemotherapy. Radiation doses prescribed to the planning tumor volume of the gross disease, high-risk clinical tumor volume, and low-risk clinical tumor volume were 66 to 70 Gy, 54 to 60 Gy, and 50–54 Gy, respectively. Results:With a median follow-up of 39 months (range, 7–77 months), 6 patients had locoregional relapse: 1 local only, 1 locoregional, and 4 regional only. Five patients had distant failure. Five of 6 total deaths were cancer related. The 3-year estimated local control, regional control, metastasis-free survival, disease-free survival, and overall survival were 96.5%, 98%, 94.8%, 90.7%, and 95.8%, respectively. No significant difference in treatment outcome was demonstrated in patients treated with or without chemotherapy of any schedule. Conclusions:IMRT without concurrent chemotherapy provides good outcome for patients with stage IIB NPC with acceptable toxicity. Neoadjuvant chemotherapy did not appear to provide significant additional benefit for this patient subgroup. Further investigation in the prospective setting is warranted to explore the role of systemic agents in the treatment of NPC with limited primary disease and cervical lymphadenopathy when IMRT is used.

Retropharyngeal nodal metastasis related to higher rate of distant metastasis in patients with N0 and N1 nasopharyngeal cancer

Retropharyngeal lymph node (RLN) staging in nasopharyngeal carcinoma (NPC) can be controversial.

Outcome of patients with nasal natural killer (NK)/T-cell lymphoma treated with radiotherapy, with or without chemotherapy†

This study reviews the outcome of patients with nasal natural killer (NK)/T‐cell lymphoma treated at the Therapeutic Radiology Department, National Cancer Centre, Singapore, from 1997 to 2003.

Combined high-dose radiation therapy and systemic chemotherapy improves survival in patients with newly diagnosed metastatic nasopharyngeal cancer.

ObjectivesTo investigate the efficacy of high-dose radiation therapy (RT) to the primary and regional disease in combination with systemic chemotherapy and local treatment to metastatic foci in patients with newly diagnosed metastatic nasopharyngeal carcinoma (NPC). MethodsOne hundred and five consecutive patients with pathologically confirmed NPC with distant metastasis at diagnosis seen between 1995 and 2002 were reviewed. All were offered cisplatin-based chemotherapy, high-dose RT (>30 Gy) to the head and neck region, and active treatment to the metastatic foci. ResultsPatients’ median age was 46 years, and all had a Karnofsky Performance Score of ≥70. Eighty-nine patients (85%) had metastases confined to 1 organ. Ninety-six patients (91%) received at least 1 cycle of chemotherapy and 71 (68%) received greater than 65 Gy of radiation to the head and neck region. With a median follow-up time of 22 months (range: 2 to 142 mo), 90 patients had deceased, and the median survival time of the entire group was 25 months. The 2 and 5-year estimated overall survival rates were 50% and 17%, respectively. Radiation dose of greater than 65 Gy to the primary region (P = 0.05) and number of organs with metastases (single vs. multiple) (P = 0.002) were independent predictive factors for overall survival on log-rank tests. Only moderately severe acute toxicities, such as Radiation Therapy Oncology Group grade 3 mucositis, skin desquamation, and leukocytopenia were observed. No patient experienced grade 4 acute toxicities. ConclusionsHigh-dose RT is indicated for local disease control in patients with metastatic NPC, and may improve survival when actively used with systemic chemotherapy and local treatment for metastatic foci. Patients with single-organ metastases have a better prognosis as compared with those with more widespread metastases.

Comparison of Combined X-Ray Radiography and Magnetic Resonance (XMR) Imaging–Versus Computed Tomography–Based Dosimetry for the Evaluation of Permanent Prostate Brachytherapy Implants

PURPOSEnTo present a method for the dosimetric analysis of permanent prostate brachytherapy implants using a combination of stereoscopic X-ray radiography and magnetic resonance (MR) imaging (XMR) in an XMR facility, and to compare the clinical results between XMR- and computed tomography (CT)-based dosimetry.nnnMETHODS AND MATERIALSnPatients who had received nonstranded iodine-125 permanent prostate brachytherapy implants underwent XMR and CT imaging 4 weeks later. Four observers outlined the prostate gland on both sets of images. Dose-volume histograms (DVHs) were derived, and agreement was compared among the observers and between the modalities.nnnRESULTSnA total of 30 patients were evaluated. Inherent XMR registration based on prior calibration and optical tracking required a further automatic seed registration step that revealed a median root mean square registration error of 4.2 mm (range, 1.6-11.4). The observers agreed significantly more closely on prostate base and apex positions as well as outlining contours on the MR images than on those from CT. Coefficients of variation were significantly higher for observed prostate volumes, D90, and V100 parameters on CT-based dosimetry as opposed to XMR. The XMR-based dosimetry showed little agreement with that from CT for all observers, with D90 95% limits of agreement ranges of 65, 118, 79, and 73 Gy for Observers 1, 2, 3, and 4, respectively.nnnCONCLUSIONSnThe study results showed that XMR-based dosimetry offers an alternative to other imaging modalities and registration methods with the advantages of MR-based prostate delineation and confident three-dimensional reconstruction of the implant. The XMR-derived dose-volume histograms differ from the CT-derived values and demonstrate less interobserver variability.

Concurrent chemoradiotherapy incorporating high-dose rate brachytherapy for locally advanced cervical carcinoma: survival outcomes, patterns of failure, and prognostic factors.

Background: This is a retrospective study evaluating the survival outcomes, patterns of failure, and prognostic factors of chemoradiotherapy incorporating high-dose rate brachytherapy in the treatment of locally advanced cervical cancer. Methods: A review of 120 consecutive patients with Federation Internationale de Gynecologie et dObstetrique (FIGO) stages IB2 to IVA cervical cancer treated with concurrent cisplatin-based chemoradiotherapy between April 1999 and January 2005. Overall (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. Results: The 5-year OS and DFS rates were, respectively, 65.0% (35.0% IB2, 65.7% IIA-B, 71.0% IIIA-B, and 40.0% IVA) and 57.3% (30.0% IB2, 58.2% IIA-B, 64.0% IIIA-B, and 40.0% IVA). Most patients had squamous cell carcinoma (89.2%) and belonged to FIGO stages IIB (40.8%) and IIIB (30.8%). All but 4 patients completed the planned radiotherapy regimen. There were 48 documented recurrences, of which 13 were locoregional only, 26 were distant only, and 9 were both sites. Five patients (4.2%) experienced late grade 3 to 4 gastrointestinal toxicity. On multivariate analysis, a preradiotherapy hemoglobin level of less than 10 g/dL and tumor size of 4 cm or greater or bulky on computed tomography were independently significant variables for OS, whereas a nadir hemoglobin level of less than 10 g/dL and presence of radiologically enlarged pelvic or paraaortic lymph nodes were independently significant variables for DFS. Conclusions: We conclude that this regimen is efficacious and feasible, but the safety profile about concurrent administration of high-dose rate brachytherapy and chemotherapy should be studied further. Finally, for cervical cancer patients selected for nonsurgical treatment, radiological assessment of tumor size and lymph node status can provide valuable prognostic information over and above FIGO staging alone.

Long‐term outcomes after reirradiation in nasopharyngeal carcinoma with intensity‐modulated radiotherapy: A meta‐analysis

The purpose of this clinical review was to summate the published data for the long‐term outcomes of reirradiation with intensity‐modulated radiotherapy (IMRT) for locally recurrent nasopharyngeal carcinoma (NPC).

A phase II trial of preoperative concurrent chemotherapy and dose escalated intensity modulated radiotherapy (IMRT) for locally advanced rectal cancer

Objectives: To determine the pathological response rates and toxicity and in patients with locally advanced rectal cancer treated with concurrent capecitabine and dose escalated intensity modulated radiotherapy (IMRT) Methods: Patients with stage II or III adenocarcinoma of the rectum were treated with preoperative concurrent capecitabine and IMRT. Dose of capecitabine was 825mg/m2, 5 days a week for 5 weeks. IMRT was used to deliver a dose of 45Gy in 25 fractions (1.8Gy per fraction daily, 5 days a week over 5 weeks) to the regional lymphatics and areas at risk of harbouring microscopic disease. A concomitant synchronous integrated boost (SIB) to the gross tumour with a margin to a total dose of 55Gy in 25 fractions was also delivered in the same period. TME surgery was performed 8 weeks after preoperative therapy. The primary endpoint is pathological complete response rate (pCR) and the secondary endpoint was downstaging rates, Sphincter preservation rates (SPR), disease free survival (DFS) at 2 years and toxicity graded using the CTCAE v3.0. Results: Twenty three patients were enrolled. Three were not evaluable; one did not complete treatment due to logistic issues and two declined surgery. The remaining 20 patients completed preoperative chemoIMRT followed by TME surgery. At a median follow-up of 38.2 months (17.5-53.2 months), 90% (18 of 20) patients were alive. The 2 year overall survival and DFS were 90% and 90% respectively. 35%(7/20) of patients had a pCR. 65% (13 of 20) patients had successful downstaging of their rectal tumours. There was no local recurrence. Sphincter preservation rate was 85%. Treatment was well tolerated with only one patient (5%) having Grade 3 radiation proctitis. Conclusions: Preoperative concurrent capecitabine and dose escalated IMRT is well tolerated and results in high rates of pCR. A randomized trial comparing this regimen with standard 3D conformal chemoradiotherapy is warranted.