Local Failure-free Rate Research Articles

Treatment results for nasopharyngeal carcinoma in the modern era: The Hong Kong experience

To analyze the treatment results achievable for nasopharyngeal carcinoma in the modern era to identify the key failures for future improvement and to provide an updated baseline for future trials. The results of 2687 consecutive patients treated at all public oncology centers in Hong Kong during 1996-2000 were retrospectively analyzed. The stage distribution (by American Joint Committee on Cancer and International Union Against Cancer staging system, 1997) was 7% Stage I, 41% Stage II, 25% Stage III, and 28% Stage IVA-B. All patients were irradiated with 6-MV photons and the median total dose was 66 Gy. Only 23% of patients had additional treatment with chemotherapy. The 5-year local, nodal, and distant failure-free rates were 85%, 94%, and 81%, respectively; patients with local failure had significantly higher risk of nodal and distant failures. The 5-year progression-free, overall, and cancer-specific survival rates were 63%, 75%, and 80%, respectively. The presenting stage was the most important prognostic factor for all endpoints: with overall survival decreasing from 90% for Stage I to 58% for Stage IVA-B. The results achieved by the 2070 patients treated by radiotherapy alone were almost identical to that of the whole series, the distant failure-free rate among patients with locoregional control was 89% for Stage I-II and 75% for Stage III-IVB. The 860 patients (32%) staged with magnetic resonance imaging achieved significantly better results than those staged by computed tomography, the overall survival being 93% vs. 83% for Stages I-II, and 72% vs. 63% for Stages III-IVB (p = 0.001). Treatment results for nasopharyngeal carcinoma have substantially improved in the modern era; future trials should be based on updated baseline results. Further reduction of distant failure is important for future breakthrough, particularly for patients with advanced disease.

In response to Dr. Önal et al.

We appreciate the interest and comments from Dr. Önal et al. We have repeated the analyses with 20 cm3 as the cutoff value. The results are shown in Table 1, Table 2. On the whole, the trend of the comparisons was essentially the same. However, the cutoff value of 20 cm3 was less sensitive in differentiating the good and poor prognostic groups in T1–2 disease patients. The local failure-free rate became insignificant in the subgroup analyses. Abbreviations: AJCC = American Joint Committee on Cancer, 5th ed; GTV-P = gross tumor volume of primary tumor. Abbreviations: Group V-L = patients with primary tumor volume ≥20 cm3; Group V-S = patients with primary tumor volume <20 cm3; LFFR = local failure-free rate; OS = overall survival; PFS = progression-free survival. Data presented as percentages. In regards to Sze et al.: Primary tumor volume of nasopharyngeal carcinoma: Prognostic significance for local control (Int J Radiat Oncol Biol Phys 2004;59:21–27)International Journal of Radiation Oncology, Biology, PhysicsVol. 61Issue 2PreviewWe read with great interest the article by Sze et al. (1). The authors concluded that the gross tumor volume of the primary tumor and involved retropharyngeal nodes (GTV-P) is a strongly significant prognostic factor for local control. Patients were stratified into two groups of GTV-P—<15 cm3 and ≥15 cm3. The local failure–free survival and progression-free survival were found significantly improved in the GTV-P <15 cm3 group. Full-Text PDF

Primary tumor volume of nasopharyngeal carcinoma: prognostic significance for local control

Purpose To study the prognostic significance of primary tumor volume on local control of nasopharyngeal carcinoma. Methods and materials Between 1998 and 2001, 308 consecutive patients with nasopharyngeal carcinoma treated with radical intent were staged with MRI. On the basis of the extent of tumor infiltration outlined by a diagnostic radiologist, the gross tumor volume of the primary and involved retropharyngeal nodes (GTV-P) was delineated by a radiation oncologist for three-dimensional conformal radiotherapy to the nasopharyngeal region using the Helax-TMS Planning System. All patients were treated with 2 Gy daily to a total dose of 70 Gy in 6–7 weeks. Additionally, chemotherapy was given to 128 patients (42%). Results The median GTV-P for the whole series was 22 cm 3 (range, 1.4–218 cm 3). Although the GTV-P varied substantially within each T stage, the overall correlation between these two parameters was strongly significant ( p <0.01), with the median GTV-P 2.7 cm 3 for T1, 13.2 cm 3 for T2, 28.1 cm 3 for T3, and 65.5 cm 3 for T4. With a median follow-up of 1.9 years (range, 0.1–3.9 years), the 3-year local failure-free rate was 87%. The 3-year local failure-free rate was 97% for patients with a GTV-P <15 cm 3 compared with 82% for those with a GTV-P ≥15 cm 3 ( p <0.01). On multivariate analysis (with T stage as a covariate), GTV-P remained an independent prognostic factor for the local failure-free rate (hazard ratio, 1.01; 95% confidence interval, 1.00–1.02; p <0.01). Conclusion Our data suggested that GTV-P is a strongly significant factor for predicting local control of nasopharyngeal carcinoma. The risk of local failure was estimated to increase by 1% for every 1 cm 3 increase in primary tumor volume.

Post-mastectomy radiotherapy after immediate autologous breast reconstruction in primary treatment of breast cancers.

To assess the clinical outcome of breast cancer patients with immediate autologous breast reconstruction and post-mastectomy radiotherapy (PMRT) as primary treatment. Twenty-five women with breast cancer treated with immediate autologous breast reconstruction and post-mastectomy radiotherapy as primary treatment between 1995 and 2001 in Pamela Youde Nethersole Eastern Hospital of Hong Kong were retrospectively studied. Radiation doses of 50 Gy (in 2 Gy daily fraction) were given to the reconstructed breasts, except one who was given 45 Gy (in 1.8 Gy daily fraction). Nine women (36%) were treated without bolus, whereas the other 16 women (64%) were treated with 0.5 cm thick bolus on alternate days. The main outcome measures include local control, treatment complications and cosmetic outcome. Median follow-up was 3.7 years (range: 1.0-6.6 years). Two women (8%), who were treated without bolus, developed chest wall recurrences. The overall 5-year, actuarial, local failure-free rate and disease-specific survival rate were 89.8% and 77.9%, respectively. Apart from mild acute skin reactions, no significant acute radiotherapy side-effects were observed. No flap necrosis or flap loss was seen. The cosmesis of the reconstructed breasts were rated as good to excellent in 85% of the surviving patients. There was no observed adverse effect on cosmesis by adding bolus on alternate days. PMRT after immediate autologous tissue-flap breast reconstruction is well tolerated and is not associated with increased incidence of complications. Adding 0.5 cm bolus on alternate days might improve local control without causing adverse cosmetic effect. The concern of adverse effects of radiotherapy should not exclude the choice of immediate breast reconstruction in suitable patients.

Prognostic influence of parapharyngeal space involvement in nasopharyngeal carcinoma

Purpose: To assess the prognostic influence of parapharyngeal space involvement in nasopharyngeal carcinoma (NPC).Methods and Materials: From January 1987 to December 1994, 197 untreated NPC patients were examined by CT scan before treatment. The parapharyngeal space was separated into pre-styloid and post-styloid compartments on axial images by the styloid process. Potentially significant parameters were analyzed by both univariate and multivariate methods using SPSS 8.0 software.Results: The actual survival, disease-free survival, and local failure-free rates were affected by the presence of parapharyngeal space involvement (p = 0.0115, p = 0.0035, p = 0.0367, respectively). The 5-year actual survival, disease-free survival, and the local failure–free rates in the patients without parapharyngeal space disease, or with pre-styloid and post-styloid compartment involvement were 87.9%, 88.0%, 96.9% and 75.0%, 71.2%, 93.7% and 60.5%, 57.7%, 86.8%, respectively. Parapharyngeal space involvement correlated well with lymphadenopathy and advanced N disease. Distant metastasis is more likely in the presence of obvious post-styloid compartment involvement (p = 0.0153). Age is a strong prognostic factor for survival.Conclusion: Parapharyngeal tumor involvement has significant predictive value. The parapharyngeal space involvement affects local tumor failure, regional tumor failure, and distant metastasis. Its survival rate is low

INTERSTITIAL BRACHYTHERAPY FOR PENILE CANCER:

Interstitial brachytherapy is an effective organ sparing treatment for localized penile squamous cell carcinoma. We report results in 30 patients. From September 1989 to November 2000, 30 men with penile squamous cell carcinoma were treated with primary brachytherapy. Tumor size was 2 to 3 cm. in 8 and greater than 3 cm. in 14 (maximum 5 cm.). Tumor was well differentiated in 11 patients, moderately in 10, poorly in 2 and unspecified in 6. Histology was verrucous in 1 patient. All implants complied with the Paris system of dosimetry, 26 of 30 with rigid steel needles held in a 3-dimensional array. The prescribed dose was 60 Gy. delivered at an average dose rate of 68 cGy. hourly for an implant duration of 93 hours. Median followup was 34 months. There have been 4 local failures yielding an actuarial local failure-free rate of 85% at 2 years (standard error 8%) and 76% at 5 years (11%). Each local failure was salvaged with penectomy (partial in 2 cases). There have been 4 isolated regional failures, involving 1 to 3 nodes, 3 moderately and 1 poorly differentiated, salvaged with groin dissection. Two patients with moderately differentiated T1 squamous cell carcinoma who died of metastatic disease after inoperable regional and subsequent distant failure. No well differentiated tumors failed regionally or distantly. Three men died of other causes with no evidence of recurrence. Function and cosmesis after implantation have been generally good. Some telangiectasia and pigmentation changes were common. Two men complained of loss of potency, 3 required dilatation for meatal stenosis and 1 underwent partial penectomy for radiation necrosis. Brachytherapy provides excellent local control of T1 to T2 penile squamous cell carcinoma, with only 1 of 30 patients requiring partial penectomy for radionecrosis. Despite excellent local control, 50% of moderately or poorly differentiated tumors recurred distantly or regionally. We recommend planned staging superficial inguinal node dissection 3 months after implantation for moderately and/or poorly differentiated tumors with clinically negative groins.

INTERSTITIAL BRACHYTHERAPY FOR PENILE CANCER: AN ALTERNATIVE TO AMPUTATION

Interstitial brachytherapy is an effective organ sparing treatment for localized penile squamous cell carcinoma. We report results in 30 patients. From September 1989 to November 2000, 30 men with penile squamous cell carcinoma were treated with primary brachytherapy. Tumor size was 2 to 3 cm. in 8 and greater than 3 cm. in 14 (maximum 5 cm.). Tumor was well differentiated in 11 patients, moderately in 10, poorly in 2 and unspecified in 6. Histology was verrucous in 1 patient. All implants complied with the Paris system of dosimetry, 26 of 30 with rigid steel needles held in a 3-dimensional array. The prescribed dose was 60 Gy. delivered at an average dose rate of 68 cGy. hourly for an implant duration of 93 hours. Median followup was 34 months. There have been 4 local failures yielding an actuarial local failure-free rate of 85% at 2 years (standard error 8%) and 76% at 5 years (11%). Each local failure was salvaged with penectomy (partial in 2 cases). There have been 4 isolated regional failures, involving 1 to 3 nodes, 3 moderately and 1 poorly differentiated, salvaged with groin dissection. Two patients with moderately differentiated T1 squamous cell carcinoma who died of metastatic disease after inoperable regional and subsequent distant failure. No well differentiated tumors failed regionally or distantly. Three men died of other causes with no evidence of recurrence. Function and cosmesis after implantation have been generally good. Some telangiectasia and pigmentation changes were common. Two men complained of loss of potency, 3 required dilatation for meatal stenosis and 1 underwent partial penectomy for radiation necrosis. Brachytherapy provides excellent local control of T1 to T2 penile squamous cell carcinoma, with only 1 of 30 patients requiring partial penectomy for radionecrosis. Despite excellent local control, 50% of moderately or poorly differentiated tumors recurred distantly or regionally. We recommend planned staging superficial inguinal node dissection 3 months after implantation for moderately and/or poorly differentiated tumors with clinically negative groins.

Retrospective analysis on treating nasopharyngeal carcinoma with accelerated fractionation (6 fractions per week) in comparison with conventional fractionation (5 fractions per week): report on 3-year tumor control and normal tissue toxicity

Background and purpose: To assess the therapeutic gain achieved by accelerated fractionation for non-keratinizing/undifferentiated nasopharyngeal carcinoma (NPC).Materials and methods: During January 1994 to October 1997, 325 patients were treated to a total dose of 66 Gy in 33–37 fractions: 167 (irradiated before mid-January 1996) with 5 daily fractions (CF) and subsequent 158 with 6 daily fractions (AF) per week. Their median treatment times were 46 and 39 days, respectively. Additional boost to parapharyngeal extension had been given to 181 and Cisplatin-based chemotherapy to 57 patients (24 concurrent with radiotherapy).Results: The AF group had significantly higher progression-free rate than the CF group (74 vs. 63% at 3 years, P=0.02 by the log-rank test). However, the difference in disease-specific survival (86 vs. 80%, P=0.39) and overall survival (81 vs. 78%, P=0.9) did not reach statistical significance. Strongly significant improvement in local failure-free rate was achieved for patients with T3–4 tumors (87 vs. 62%, P<0.01). Multivariate analyses showed that fractionation was an independent significant factor for overall progression: hazard ratio=0.63, 95% confidence interval: 0.41–0.98, P=0.04. Among the 268 patients treated with radiotherapy alone, those treated by AF had significantly higher incidence of acute reaction grade ≥3 (72 vs. 13%, P<0.01). However, all patients completed the scheduled dose without excessive prolongation, and no significant increase in late complications was observed (20 vs. 15% at 3 years, P=0.19).Conclusions: The current analyses suggested that acceleration to 6 daily fractions per week could significantly improve the progression-free rate for NPC without excessive late toxicity. Improvement in local control was confined to T3–4 tumors.

Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976–1985: Overall survival and patterns of failure

This is a retrospective analysis of 5037 patients with squamous cell carcinoma of the nasopharynx treated during the years 1976–1985. The stage distribution according to Ho's classification was 9% Stage 1, 13% II, 50% III, 22% IV, and 6% Stage V. Only 4488 (89%) patients had a full course of megavoltage radiation therapy. The median equivalent dose to the nasopharyngeal region was 65 Gy and cervical region in node-positive patients 53 Gy. Seventy percent (906/1290) of the node-negative patients had no prophylactic neck irradiation. The overall actuarial 10-year survival rate was 43%, and the corresponding failure-free survival 34%. Altogether, 4157 (83%) patients achieved complete remission lasting more than 6 months, but 53% (2205/4157) of them relapsed after a median interval of 1.4 years. The 10-year actuarial local, regional, and distant failure-free rates were 61%, 64%, and 59%, respectively. Thirty-eight percent ( 338 891 ) of all patients with local recurrence achieved second local remission. The local complete remission rate with aggressive re-irradiation alone was 47% ( 333 706 ). But 37% ( 124 338 ) of the responders recurred the second time. The incidence of distant failure correlated significantly with both the N-stage and the T-stage, with the highest (57%) occurring in patients with N3 disease. The incidence of nodal relapse in node-negative patients was 11% ( 44 384 ) among those given prophylactic neck irradiation, but 40% ( 362 906 ) among those without. Therapeutic irradiation achieved a complete regional remission rate of 90% ( 306 339 ). However, despite successful salvage, these patients had a significantly higher distant failure rate than those without nodal relapse, even if they remained local-failure-free (21% vs 6%). Patients treated during 1981–1985 achieved significantly better treatment results than those treated during 1976–1980, especially in terms of the overall survival (57% vs 47% at 5-year), the overall failure-free survival (42% vs 35% at 5-year), and the local failure-free rate (70% vs 63% at 5-year). The possible contributing factors are discussed.