Nodal Control Rates Research Articles

Chemoradiation for Advanced Head and Neck Cancer: Potential for Improving Results to Match Those of Current Treatment Modalities for Early-Stage Tumors—Long-Term Results of Hyperfractionated Chemoradiation With Carbogen Breathing and Anemia Correction With Erythropoietin

To attempt to improve results of chemoradiation for head and neck cancer. From March 1996 to April 2007, 98 patients with head and neck cancer (15 Stage III and 83 Stage IV) were treated with a twice-daily hyperfractionated schedule. Eleven patients presented with N0, 11 with N1, 13 with N2A, 17 with N2B, 24 with N2C, and 22 with N3. Each fraction of treatment consisted of 5 mg/m(2) of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m(2) of carboplatin plus 8050 cGy in 7 weeks. Anemia was corrected with erythropoietin. Ninety-six patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Local toxicity remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Ninety-seven complete responses were achieved. After 11 years of follow-up (median, 81 months), actuarial locoregional control, cause-specific survival, overall survival, and nodal control rates at 5 and 10 years were, respectively, 83% and 83%, 68% and 68%, 57% and 55%, and 100% and 100%. Median follow-up of disease-free survivors was 80 months. No significant differences in survival were observed between the different subsites or between the pretreatment node status groups (N0 vs. N+, N0 vs. N1, N0 vs. N2A, N0 vs. N2B, N0 vs. N2C, and N0 vs. N3). Improving results of chemoradiation for advanced head and neck cancer up to the level obtained with current treatments for early-stage tumors is a potentially reachable goal.

Involved-Field Radiation Therapy for Inoperable Non–Small-Cell Lung Cancer

Dose escalation has been shown to improve local control in non-small-cell lung cancer (NSCLC) treated with definitive radiation therapy, but with increased complications. We implemented the use of involved-field radiotherapy (IFRT) in an effort to reduce toxicity while treating the gross tumor to higher doses. This analysis reports failure rates in uninvolved nodal regions with the use of IFRT. A total of 524 patients with NSCLC treated with three-dimensional conformal radiotherapy at Memorial Sloan-Kettering Cancer Center between 1991 and 2005 were reviewed. Only lymph node regions initially involved with tumor by either biopsy or radiographic criteria were included in the clinical target volume. Elective nodal failure (ENF) was defined as a recurrence in an initially uninvolved lymph node in the absence of local failure. Only 32 patients (6.1%) with ENF were identified. The 2-year actuarial rates of elective nodal control and primary tumor control were 92.4% and 51%, respectively, with a median follow-up of 41 months in survivors. In patients who achieved local disease control, the 2-year elective nodal control rate was 91%. The median time to ENF was 6 months (range, 0 to 56 months). Many patients experienced treatment failure in multiple lymph node regions simultaneously. The use of IFRT did not cause a significant amount of failure in lymph node regions not included in the tumor volume. Therefore, IFRT remains an acceptable method of treatment that allows for dose escalation while minimizing toxicity.

Postoperative Radiotherapy for Maxillary Sinus Cancer: Long-Term Outcomes and Toxicities of Treatment

To determine the effects of three changes in radiotherapy technique on the outcomes for patients irradiated postoperatively for maxillary sinus cancer. The data of 146 patients treated between 1969 and 2002 were reviewed. The patients were separated into two groups according to the date of treatment. Group 1 included 90 patients treated before 1991 and Group 2 included 56 patients treated after 1991, when the three changes were implemented. The outcomes were compared between the two groups. No differences were found in the 5-year overall survival, recurrence-free survival, local control, nodal control, or distant metastasis rates between the two groups (51% vs. 62%, 51% vs. 57%, 76% vs. 70%, 82% vs. 83%, and 28% vs. 17% for Groups 1 and 2, respectively). The three changes were to increase the portals to cover the base of the skull in patients with perineural invasion, reducing their risk of local recurrence; the addition of elective neck irradiation in patients with squamous or undifferentiated histologic features, improving the nodal control, distant metastasis, and recurrence-free survival rates (64% vs. 93%, 20% vs. 3%, and 45% vs. 67%, respectively; p < 0.05 for all comparisons); and improving the dose distributions within the target volume, reducing the late Grade 3-4 complication rates (34% in Group 1 vs. 8% in Group 2, p = 0.014). Multivariate analysis revealed advancing age, the need for enucleation, and positive margins as independent predictors of worse overall survival. The need for enucleation also predicted for worse local control. The three changes in radiotherapy technique improved the outcomes for select patients as predicted. Despite these changes, little demonstrable overall improvement occurred in local control or survival for these patients and additional work must be done.

Postoperative IMRT in head and neck cancer

BackgroundAim of this work was to assess loco-regional disease control in head and neck cancer (HNC) patients treated with postoperative intensity modulated radiation therapy (pIMRT). For comparative purposes, risk features of our series have been analysed with respect to histopathologic adverse factors. Results were compared with an own historic conventional radiation (3DCRT) series, and with 3DCRT and pIMRT data from other centres.Between January 2002 and August 2006, 71 patients were consecutively treated with pIMRT for a squamous cell carcinoma (SCC) of the oropharynx (32), oral cavity (22), hypopharynx (7), larynx (6), paranasal sinus (3), and an unknown primary, respectively. Mean and median follow up was 19 months (2–48), and 17.6 months. 83% were treated with IMRT-chemotherapy. Mean prescribed dose was 66.3 Gy (60–70), delivered with doses per fraction of 2–2.3 Gy, respectively.Results2-year local, nodal, and distant control rates were 95%, 91%, and 96%, disease free and overall survival 90% and 83%, respectively. The corresponding survival rates for the subgroup of patients with a follow up time >12 months (n = 43) were 98%, 95%, 98%, 93%, and 88%, respectively. Distribution according to histopathologic risk features revealed 15% and 85% patients with intermediate and high risk, respectively. All loco-regional events occurred in the high risk subgroup.ConclusionSurgery followed by postoperative IMRT in patients with substantial risk for recurrence resulted in high loco-regional tumor control rates compared with large prospective 3DCRT trials.

Regional nodal recurrence in breast cancer patients treated with conservative surgery and radiation therapy (BCS+RT)

To review regional nodal (RN) management and identify predictors of RN relapse in patients treated with breast conserving surgery and radiation therapy (BCS+RT). Patients with Stage I and II breast cancer (N = 1920) underwent BCS+RT from 1973 to 2003. Patients undergoing RN were treated with a median dose of 46 Gy. Patients undergoing axillary dissection (AXD, N = 1330) were treated to the breast alone if node-negative (N = 984), and to the breast and supraclavicular fossa if node-positive (N = 346). Patients who did not undergo AXD (N = 590) were treated with RT to the supraclavicular fossa and axilla. Sentinel node biopsy (SNB) was performed on 126 patients. SN-negative patients (N = 110) were treated with tangents only. There were 16 SN-positive patients who did not undergo complete AXD and were treated with RT. As of September 2005, there have been 36 RN relapses for an actuarial nodal control rate (NCR) of 98% at 10 years. There was no difference in NCR between those undergoing AXD (NCR = 97.4%) and those receiving RT without AXD (NCR = 97.9%). In multivariate analysis, young age, non-Caucasian race, and pathologic nodal status correlated with increased risk of nodal relapse. Of the 126 patients undergoing SNB, there was only 1 nodal recurrence. None of the 16 SN-positive patients treated with RT without AXD had nodal failure. In patients undergoing BCS+RT, both regional nodal irradiation and AXD (including SNB) resulted in equally high rates of regional nodal control. Nodal RT may also be an effective treatment for SN-positive patients.

Prognostic Value of Tumor Volume in Nasopharyngeal Carcinoma

Tumor bulk has been recognized as an important prognostic factor in the treatment of malignancy. The purpose of the present study is to investigate the prognostic value of tumor volume in nasopharyngeal carcinoma. Sixty patients with nasopharyngeal carcinoma were included in this study. Tumor contour was outlined on each of the computed tomography (CT) images using an image analyzer. The primary tumor volume (PTV) and nodal tumor volume (NTV) were calculated by a summation-of-areas technique, and the maximal perimeter of primary tumor (MPP) was measured. The loco-regional control rates and disease-specific survival rates were analyzed according to several variables. The patients had a 5-year local control rate of 75.5%, 5-year nodal control rate of 74.6%, and 5-year disease-specific survival rate of 60.2%. Large PTV (> 30 cm3) was associated with a significantly lower local control (p=0.005). Large NTV (> 5 cm3) was associated with a significantly lower nodal control (p=0.019) and lower disease-specific survival (p=0.046). Large MPP (> 18 cm) was associated with a significantly lower local control (p=0.017). In multivariate analysis, the PTV and NTV were found to be independent factors in predicting the local (p=0.015) and nodal (p=0.039) control, respectively. The NTV (p=0.012) and cranial nerve involvement (p=0.009) were factors that predicted disease-specific survival. Our results suggest that the estimation of tumor volume may identify a subgroup of patients with a greater risk of loco-regional failure and can be used to refine the current staging system.

Supracricoid partial laryngectomy with cricohyoidopexy and cricohyoidoepiglottopexy: functional and oncological results

Sixty-eight patients who presented with glottic and glottosupraglottic squamous cell carcinoma and who were managed in this department with supracricoid partial laryngectomy (SCPL) with either cricohyoidoepiglottopexy (CHEP) or cricohyoidopexy (CHP), were retrospectively reviewed. The authors analysed the functional and oncological results of the patients. The median follow-up period was 62 months. The average times until decannulation and nasogastric feeding tube removal were 27.7 and 26.4 days, respectively. All patients were successfully decannulated. All patients were able to swallow, but one patient was unable to swallow and had recurrent aspiration. Better functional results were achieved in patients managed with CHEP procedure than the patients managed with CHP procedure. The five-year absolute and cause-specific actuarial survival rates (Kaplan-Meier method) were 78.6 per cent and 93.9 per cent, respectively. The five-year actuarial local control and nodal control rates were 89.5 per cent and 90.4 per cent, respectively. Local recurrence was statistically more likely in patients with positive resection margins (p <0.006). Overall, local control and laryngeal preservation were achieved in 95.6 per cent and 89.7 per cent, respectively. Supracricoid partial laryngectomy procedures (CHEP and CHP) are possible alternatives to total laryngectomy in the treatment of selected advanced glottic and glottosupraglottic carcinomas.

Treatment outcome for synchronous locoregional failures of nasopharyngeal carcinoma.

To review the outcome and evaluate the prognostic factors in the treatment of synchronous locoregional failures of nasopharyngeal carcinoma (NPC). We reviewed the records of 43 patients with synchronous locoregional failures of NPC who received salvage treatment or chemotherapy between November 1986 and January 2001. The recurrent disease was stage II in 61%, stage III in 30%, and stage IV in 9%. The local disease was rT1-2 in 67% and rT3-4 in 33%, and the regional disease was rN1 in 91% and rN2 in 9%. Persistent disease, defined as failures within 4 months of completion of primary radiotherapy, occurred in 53.5% and recurrent disease in 46.5%. Seventeen patients received surgery for regional and/or local failures with or without combined radiotherapy (ST group), 14 patients received reirradiation to both local and regional disease (RT group), and 12 patients received palliative chemotherapy only (CT group). The median follow-up was 18 months (range, 4-153) and for the surviving patients it was 29 months (range, 6-153). The 3-year relapse-free survival (RFS) rate and disease-specific survival (DSS) rate after salvage treatment or chemotherapy were 17% and 38%, respectively. The 3-year RFS rates in stage II, III, and IV disease were 25%, 8%, and 0%, respectively. The corresponding 3-year DSS rates were 43%, 28%, and 38%. The 3-year RFS rates in the ST, RT, and CT group were 39%, 7%, and 0%, respectively. The corresponding 3-year DSS rates were 55%, 25%, and 25%. Patients whose local disease was treated by surgical resection had a 3-year local control rate of 71% compared with 38% by reirradiation using brachytherapy or external radiotherapy. For regional disease, the 3-year nodal control rate after radical neck dissection was 65% compared with 24% by reirradiation. Further locoregional failure represents the major failure pattern, and the proportion of patients who had further local, regional, and both locoregional failures were 16%, 9%, and 53%, respectively. Distant metastasis occurred in 30% of patients, and only 5% had isolated distant metastasis in the absence of locoregional failures. On multivariate analysis, treatment by reirradiation or chemotherapy alone and rN2 disease were independent factors that predicted poor survival, whereas treatment by reirradiation or chemotherapy alone was the only independent factor that predicted further relapse or failure. Proper selection of patients for aggressive salvage treatment and individualization of treatment are important in managing patients with synchronous locoregional failures of NPC. A significant proportion of patients with early stage locoregional failures can still achieve long-term disease control and survival after aggressive salvage treatment using surgery with or without combined radiotherapy. In patients with more advanced disease, treatment by reirradiation alone or palliative chemotherapy is largely ineffective and is associated with a poor outcome.

Sphincter-sparing local excision and adjuvant radiation for anal-rectal melanoma.

To evaluate the outcome and toxicity of a sphincter-sparing treatment strategy in the management of patients with anal-rectal melanoma. Between 1989 and 2000, 23 patients with invasive anal-rectal melanoma were managed with sphincter-sparing surgical resection and adjuvant radiation. Surgery consisted of primary local excision, as well as dissection for patients with documented regional nodal disease. Adjuvant radiation was delivered using a hypofractionated regimen of 30 Gy in five fractions over 2.5 weeks. Adjuvant systemic therapy was delivered to nine patients: cytotoxic chemotherapy in seven and immunotherapy in two. After a median follow-up of 32 months, 15 patients had relapsed and 15 patients had died. The actuarial 5-year overall, disease-specific, disease-free, and distant metastasis-free survival rates were 31%, 36%, 37%, and 35%, respectively. The actuarial 5-year local and regional nodal control rates were 74% and 84%, respectively. No patient had locoregional failure as the sole site of failure and no patient required salvage abdominoperineal resection (APR). By univariate analysis, patients with nodal disease at presentation had a decreased actuarial 5-year disease-specific (0% v 45%, P =.004), disease-free (0% v 45%, P <.001), and distant metastasis-free survival (0% v 42%, P <.001). The actuarial complication-free survival rate was 71%. Two patients developed mild scrotal edema (grade 1), and four patients developed moderate proctitis requiring prolonged medical management (grade 2). Sphincter-sparing local excision and adjuvant radiation is well tolerated and can effectively control local-regional disease while avoiding the functional morbidity of APR.

Epithelioid sarcoma: results of conservative surgery and radiotherapy

Purpose: To determine the outcome and prognostic factors for patients with localized epithelioid sarcoma treated with conservative surgery and radiotherapy (RT).Methods and Materials: The medical records of 24 patients with nonmetastatic epithelioid sarcoma treated with conservative surgery and RT were reviewed. Preoperative RT was given to 3 patients (median 46.4 Gy) and postoperative RT to 21 patients (median 64.5 Gy). A local (limb-sparing) surgical procedure was performed in all patients.Results: At a median follow-up of 131 months, 14 patients had relapsed and 13 patients had died. The actuarial overall and disease-free survival rate at 10 years was 50% and 37%, respectively. Local, nodal, and metastatic failure occurred in 7, 4, and 10 patients, respectively, yielding a 10-year actuarial local, nodal, and metastatic control rate of 63%, 81%, and 56%, respectively. Univariate analysis revealed that size ≤5 cm and extremity location were favorable prognostic factors for overall, disease-free, and metastasis-free survival. The actuarial 5-year overall, disease-free, and metastasis-free survival rate was 79% vs. 25% (p = 0.002), 51% vs. 13% (p = 0.03), and 79% vs. 13% (p <0.001), respectively, for lesion size ≤5 vs. > 5 cm. The actuarial 5-year overall, disease-free, and metastasis-free survival rate was 77% vs. 39% (p = 0.002), 56% vs. 0% (p = 0.01), and 78% vs. 17% (p = 0.01), respectively, for extremity vs. nonextremity location. Multivariate analysis of the factors correlating with the overall, disease-free, and metastasis-free survival confirmed the favorable prognostic significance of small lesion size. The prognostic significance of extremity location on univariate analysis was explained by an imbalance in the mean tumor sizes.Conclusions: Epithelioid sarcoma is an aggressive soft-tissue sarcoma, with high rates of local and distant relapse. Local control with conservative surgery and RT compares favorably to published surgical series. The poor outcome for tumors ≥5 cm in size emphasizes the need for effective systemic therapy.

Phase III trial of high- vs. low-dose-rate interstitial radiotherapy for early mobile tongue cancer

Purpose: Early mobile tongue cancer can be controlled with interstitial radiotherapy (ISRT). We carried out a Phase III trial to compare the treatment results of low-dose-rate (LDR) ISRT and high-dose-rate (HDR) ISRT for early mobile tongue cancer. Methods and Materials: From April 1992 through October 1996, 59 patients with cancer of the early mobile tongue were registered in this Phase III study. Eight patients were excluded from the evaluation because of violations of the requirements for this study. Of 51 eligible patients, 26 patients were treated with LDR-ISRT (70 Gy/4–9 days) and 25 patients with HDR-ISRT (60 Gy/10 fractions/1 week). For the hyperfractionated HDR-ISRT, the time interval between 2 fractions was more than 6 h. Results: Five-year local control rates of the LDR and HDR groups were 84% and 87% respectively. Nodal metastasis occurred in 6 patients in each group. Five-year nodal control rates of the LDR and HDR groups were 77% and 76%, respectively. Conclusion: Hyperfractionated HDR-ISRT for early mobile tongue cancer has the same local control compared with continuous LDR-ISRT. Hyperfractionated HDR-ISRT is an alternative treatment for continuous LDR-ISRT.

Parotid-sparing irradiation for cancer of the oral cavity: maintenance of oral nutrition and body weight by preserving parotid function.

The purpose of this study was to assess the nutritional benefit of parotid-sparing irradiation, comparing the body weights of patients irradiated with parotid-sparing technique versus those irradiated with bilateral opposed photon beams, including both parotid glands in the radiation fields. One hundred fourteen patients with cancer of the oral cavity were irradiated with curative intent. Two-dimensional radiotherapy techniques sparing at least one parotid gland from the radiation beams were used to treat 31 patients (parotid-sparing techniques). Eighty-three patients were irradiated using bilateral opposed photon beams, which included both parotid glands (bilateral technique). Body weight during and after irradiation, treatment outcome, and survival were compared. Patients treated with parotid-sparing techniques maintained their nutritional intake and baseline body weight during and after irradiation. Patients treated with the bilateral technique that included both parotid glands had poor nutritional intake, leading to a more than 10% decline in their initial body weight; these patients did not regain their body weight during the 2-year follow-up period. Primary tumor control rate was higher for patients treated with parotid-sparing techniques than for patients who had both parotid glands irradiated (70% versus 48%; p = 0.05). This difference is because a higher percentage of patients treated with parotid-sparing techniques had early-stage tumors (54%) compared with patients treated with the bilateral technique (24%). When analyzed according to the tumor stage, the primary tumor control rates for patients treated with parotid-sparing techniques and for patients treated with the bilateral technique showed no difference; control rates were 93% and 87% (p = 1.00) for early-stage tumors and 42% and 36% (p = 0.75) for advanced-stage tumors, respectively. Nodal control rates in the ipsilateral side of the neck and in the contralateral side of the neck for patients treated with parotid-sparing techniques and with the bilateral technique were not significantly different-74% versus 76% (p = 0.86) and 70% versus 82% (p = 0.21), respectively. Sparing at least one parotid gland during irradiation of patients with head and neck cancer will preserve parotid function and prevent xerostomia. Patients treated with parotid-sparing techniques were able to maintain their oral nutrition and body weight, compared with patients who had both parotid glands irradiated. A higher percentage of patients treated with parotid-sparing techniques had early-stage tumors, resulting in higher rates of primary tumor control and survival in this group of patients.

Squamous cell carcinomas of the soft palate treated with radiation therapy alone or followed by planned neck dissection

Purpose: The present study presents the experience at the University of Florida with treatment of unselected patients with carcinomas of the soft palate with radiation therapy (RT) alone or followed by planned neck dissection. Methods and Materials: One hundred seven patients treated with curative intent with RT alone or followed by neck dissection from 1965 to 1996 were included in the study. All patients had follow-up for at least 2 years. No patients were lost to follow-up. Results: Local control rates at 5 years were 86% for T1, 91% for T2, 67% for T3, and 36% for T4 carcinomas. T-stage and overall treatment time significantly affected local control in multivariate analysis. Nodal control rates at 5 years were 86% for N0, 76% for N1, 61% for N2, and 67% for N3 carcinomas. Overall treatment time and planned neck dissection significantly affected nodal control in multivariate analysis. Ultimate local-regional control rates at 5 years were 90% for Stage I, 92% for Stage II, 84% for Stage III, and 60% for Stage IV disease. Overall treatment time and planned neck dissection significantly affected ultimate local-regional control in multivariate analysis. The overall survival rate at 5 years was 42% for all patients. Overall stage, overall treatment time, and planned neck dissection significantly affected overall survival in multivariate analysis. The cause-specific survival rate at 5 years was 70% for all patients. Overall treatment time and planned neck dissection significantly affected cause-specific survival in multivariate analysis. Three patients sustained severe postoperative complications and 3 patients sustained severe late complications. Sixteen patients had synchronous and 14 patients had metachronous carcinomas of the head and neck mucosal sites. Conclusion: For limited carcinomas of the soft palate, RT (alone or followed by planned neck dissection) results in relatively high local-regional control and survival rates. For advanced carcinomas of the soft palate, local-regional control and survival rates are relatively low and local-regional recurrence rates are substantial. Advanced carcinomas of the soft palate may be better treated with RT and concomitant chemotherapy.

Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head-and-neck mucosal site treated with radiation therapy alone or in combination with neck dissection

Purpose: The present study presents the experience at the University of Florida with treatment of patients with squamous cell carcinomas (SCC) metastatic to cervical lymph nodes from an unknown head-and-neck mucosal (H&NM) site with radiotherapy (RT) alone or in combination with neck dissection (ND). Methods and Materials: The study included 126 patients treated with curative intent from 1964 to 1997. All patients had follow-up for at least 2 years. No patients were lost to follow-up. Results: Twelve patients (10%) developed SCC in H&NM sites at 0.5 to 10.9 years (median, 1.8 years). The rate of developing carcinomas in H&NM sites at 5 years was 13%. Histologic differentiation significantly affected the rate of developing carcinomas in H&NM sites in multivariate analysis. Sixteen patients (13%) had persistent nodal disease and 12 patients (10%) developed recurrent nodal disease at 0.5 to 10.9 years (median, 1.1 years). The nodal control rate at 5 years was 78%. Nodal size, N stage, and planned ND significantly affected the rate of nodal control in multivariate analysis. Nineteen patients (15%) developed distant metastasis at 0.2–5.1 years (median, 0.9 years). The distant metastases rate at 5 years was 14%. Extracapsular extension and RT dose significantly affected the risk of distant metastases in multivariate analysis. The overall absolute survival rate at 5 years was 47%. Extracapsular extension, N stage, RT dose for H&NM sites, and planned ND significantly affected absolute survival in multivariate analysis. The rate of cause-specific survival at 5 years was 67%. Extracapsular extension, nodal size, N stage, overall treatment time, and planned ND significantly affected cause-specific survival in multivariate analysis. Eight patients (6%) had severe postoperative complications and 6 patients (5%) had severe late complications. Conclusion: The present study supports the effectiveness of RT in lowering the rate of developing carcinomas in the H&NM sites.

Axillary Recurrence Following Conservative Surgery and Radiotherapy in Early Breast Cancer

At the institute, since the late 1980s, there has been a uniform treatment protocol for the management of the regional lymph nodes in patients referred for radiotherapy following breast-conserving surgery. An analysis of 2277 consecutive patients referred for radiotherapy between 1989 and 1992, with particular reference to regional lymph node management, has been undertaken. Axillary surgery alone was used in 517 patients (23%); 1191 (52%) patients had no axillary surgery but had radiotherapy to the axilla, and infraclavicular and supraclavicular fossae by a single anterior field, delivering 40 Gy in 15 daily fractions over 3 weeks; and 474 patients (21%) had axillary surgery followed by radiotherapy. Ninety-five patients (4%) underwent no axillary treatment. There was a total of 155 axillary recurrences with a median follow-up of 5.9 years, giving an actuarial nodal control rate of 94% at 5 years (95% confidence interval (CI) 93.1–95.1). The overall survival at 5 years was 86% (95% CI 84.6–87.5). There was a trend towards improved axillary control with surgery alone compared with radiotherapy alone (4.5% versus 5.9% actuarial axillary failure rate at 5 years). An extremely low incidence of brachial plexus neuropathy secondary to radiotherapy was reported. The multidisciplinary treatment protocol used gave a high rate of regional node control, with minimal recorded morbidity.

Chemotherapy as a part of each treatment fraction in a twice‐a‐day hyperfractionated schedule: A new chemoradiotherapy approach for advanced head and neck cancer

Background Using chemotherapy as a part of each treatment fraction remains unexplored. This study integrates the concomitant administration of carboplatin with hyperfractionated irradiation by optimizing chemopotentiation through carboplatin administration with each irradiation fraction. Methods From February 1993 to August 1996, 52 patients with advanced head and neck cancer were treated on a twice-a-day chemoradiotherapy schedule. Each fraction consisted of 115 cGy preceded by 5 mg/m2 of carboplatin. Treatment was given 5 days a week up to total doses of 350 mg/m2 of carboplatin + 8050 cGy in 7 weeks. Results All (100%) of patients tolerated the treatment (83% as scheduled). Acute and late toxicities were moderate. Rates of 96% complete response (CR) and 4% partial response (PR) were achieved. At 52 months, local control and cause-specific survival rates are 72% and 59%, respectively. Nodal control rate is 95%. Conclusion These results show potential for improvement upon hyperfractionated radiotherapy alone and compare favorably with those of most reported trials. © 1998 John Wiley & Sons, Inc. Head Neck 20: 489–496, 1998.

Evaluation of cervical nodal necrosis in nasopharyngeal carcinoma by computed tomography: Incidence and prognostic significance

Purpose The purpose was to study the prognostic value of contrast-enhanced computed tomography (CT) nodal necrosis in nasopharyngeal carcinoma. Patients and Methods One hundred sixty-one patients with newly diagnosed nasopharyngeal carcinoma and nodal metastases were reviewed. Forty patients also received cisplatin-based neoadjuvant chemotherapy in addition to radiotherapy. Nodal necrosis was defined as presence of hypodense areas in more than 33% of the node. Nodal response rate to chemotherapy, overall nodal control rate, local control rate, distant failure rate, overall relapse-free survival rate, and overall and cause-specific survival rates were compared between patients with and without nodal necrosis. Multivariate analysis was also performed. Results The incidence of nodal necrosis was 22.9%. Overall nodal response rates to chemotherapy were 88.9% (8/9) in patients with nodal necrosis and 74.2% (23/31) in those without. No significant differences in nodal control rate, local control rate, distant failure rate, and overall and cause-specific survival rates were found. Five-year overall relapse-free survival rate was lower in patients with cervical nodal necrosis (36%) as compared with those without (53%, p = .04). Multivariate analysis, however, did not confirm cervical nodal necrosis to be an independent prognostic factor. Conclusions Presence of nodal necrosis in nasopharyngeal carcinoma does not affect nodal response to chemotherapy and nodal control by radiotherapy with or without chemotherapy. Cervical nodal necrosis does not appear to be an independent factor in predicting treatment outcome. Further studies to correlate nodal density with oxygenation status as well as tumor cell kinetics are warranted. © 1997 John Wiley & Sons, Inc. Head Neck 19: 266–275, 1997.

Phase III trial of high and low dose rate interstitial radiotherapy for early oral tongue cancer

Purpose: Oral tongue carcinomas are highly curable with radiotherapy. In the past, patients with tongue carcinoma have usually been treated with low dose rate (LDR) interstitial radiation. This Phase III study was designed to compare the treatment results obtained with LDR with those obtained with high dose rate (HDR) interstitial radiotherapy for tongue carcinoma.Methods and Materials: The criteria for patient selection for the Phase III study were: (a) presence of a T1T2N0 tumor that could be treated with single-plane implantation, (b) localization of tumor at the lateral tongue border, (c) tumor thickness of 10 mm or less, (d) performance status between O and 3, and (e) absence of any severe concurrent disease. From April 1992 through December 1993, 15 patients in the LDR group (70 Gy/4 to 9 days) and 14 patients in the HDR group (60 Gy/10 fractions/6 days) were accrued. The time interval between two fractions of the HDR brachytherapy was more than 6 h.Results: Local recurrence occurred in two patients treated with LDR brachytherapy but in none of the patients treated with HDR. One- and 2-year local control rates for patients in the LDR group were both 86%, compared with 100% in the HDR group (p = 0.157). There were four patients with nodal metastasis in the LDR group and three in the HDR group. Local recurrence occurred in two of the four patients with nodal metastases in the LDR group. One- and 2-year nodal control rates for patients in LDR group are were 85, compared with 79% in the HDR group.Conclusion: HDR fractionated interstitial brachytherapy can be an alternative to traditional LDR brachytherapy for early tongue cancer and eliminate the radiation exposure for medical staffs.

Clinical behavior of untreated axillary nodes after local treatment for primary breast cancer.

The purpose of this study was to examine the rate of axillary failure in patients with primary breast cancer treated without axillary dissection or radiation and to determine what factors may be associated with axillary failure. We studied 112 patients with invasive breast cancer treated for primary disease with breast-conserving surgery without axillary dissection or radiation to the breast or axilla, accrued between 1977 and 1986. Data for these patients were prospectively gathered for a research database and reviewed retrospectively to determine axillary failure. The effects of age, tumor size, estrogen receptor (ER) status, progesterone receptor (PgR) status, histologic grade, nuclear grade, and tumor emboli on time to axillary failure were examined. The median follow-up was 9.6 years. There were 26 axillary recurrences, resulting in a 10-year actuarial nodal control rate of 72%. Patients with nodal failure proceeded to axillary dissection with minimal morbidity. In both univariate and multivariate analyses, only tumor size was significantly associated with axillary failure (p = 0.04 and p = 0.06, respectively). This study demonstrates a significant effect of tumor size on axillary failure and a reasonable rate of local control in small tumors. Further research should examine the utility of axillary dissection in women with small breast cancers.

Prognostic significance of keratinization in nasopharyngeal carcinoma

Introduction: Keratinization may be a vulnerable aid in predicting response to therapy for nasopharyngeal carcinoma. Methods: The presence or absence of keratin in biopsy specimens was correlated with tumor behavior, locoregional control, patterns of failure, and survival of patients irradiated for nasopharyngeal carcinoma. Results: Patients with keratinizing squamous-cell cancers (World Health Organization [WHO] type 1) had a higher incidence (76%) of locally advanced tumors than those with nonkeratinizing (WHO type 2) and undifferentiated (WHO type 3) cancers (55%). The former group of patients had a lower incidence (29%) of lymph node metastases than the later group (70%). Primary tumor was controlled in 62% and neck nodes were controlled in 82% of all patients. Primary tumor control rates were 29% in patients with keratinizing squamous-cell cancers and 79% in those with nonkeratinizing and undifferentiated cancers ( P = .001). Nodal control rates were 76% for keratinizing squamous-cell cancer and 85% for nonkeratinizing and undifferentiated cancers ( P = .001). The incidence of distant metastases was 6% in patients with keratinizing squamous-cell cancer and 33% in those with nonkeratinizing and undifferentiated cancers ( P = .001). Patients with keratinizing squamous-cell cancers, even though they had a lower incidence of lymphatic and distant metastases, had a poorer survival rate because of a higher incidence of deaths from uncontrolled primary tumors and nodal metastases. The 5-year survival rates were 35% for all patients, 6% for those with keratinizing squamous-cell cancers, and 51% for nonkeratinizing and undifferentiated cancers respectively ( P = .001). Conclusion: Higher doses of external beam radiotherapy with or without brachytherapy boost may be needed to improve local control and survival of patients with keratinizing squamous-cell carcinoma of the nasopharynx, whereas an effective systemic therapy is needed for nonkeratinizing and undifferentiated cancers, which tend to metastasize.