5-year Locoregional Control Rates Research Articles

Association of Haemoglobin Level with Morbidity and Mortality of Patients with Locally Advanced Oesophageal Carcinoma Undergoing Radiotherapy — A Secondary Analysis of Three Consecutive Clinical Phase III Trials

Aims To investigate the strength of association between anaemia and overall survival, locoregional control, and late radiation complications in patients with locally advanced oesophageal carcinoma undergoing radiotherapy with or without chemotherapy and hyperthermia. Materials and methods Between March 1996 and December 2002, 303 patients with locally advanced squamous cell carcinoma of oesophagus enrolled in three consecutive prospective phase III trials conducted in our department were included in this study. These patients received one of the following four irradiation schedules: late course accelerated hyperfractionated (LCAF) radiotherapy alone, LCAF combined with concurrent chemotherapy, LCAF combined with hyperthermia, and continuous accelerated hyperfractionated (CAHF) radiotherapy according to each protocol. According to the haemoglobin levels measured before radiotherapy, patients were stratified to normal haemoglobin group (≥12.0 g/dl for men, or ≥11.0 g/dl for women) or anaemic group (<12.0 g/dl for men, or <11.0 g/dl for women). Overall survival, locoregional control rate and late irradiation toxicity were estimated by Kaplan–Meier method. Results Of 303 eligible patients, 243 patients (80.2%) had normal haemoglobin level and 60 patients (19.8%) were anaemic. The 5-year overall survival was 39% in patients with normal haemoglobin level, whereas, 22%, with anaemia patients ( P = 0.001). The 5-year locoregional control rate at 5 years was 68% in patients with normal haemoglobin, versus 62%, with anaemia patients ( P = 0.050). The 5-year rate of radiation toxicity of grade 3 or greater was 29% in patients with normal haemoglobin level, but it was 8%, with anaemic patients ( P = 0.033). From multivariate analyses, T stage, location of tumour and haemoglobin level were found to be independent predictors for survival. T stage, gender and haemoglobin level were independent predictors for locoregional control. It was also detected that age and haemoglobin level played as independent predictors for development of radiation toxicity. Conclusions For patients with locally advanced oesophageal carcinoma undergone irradiation, anaemia associated a statistically significant reduction in survival and locoregional control rates, but also decreased radiation toxicity rates. Therefore, haemoglobin level should be considered as a stratification variable in prospective clinical trials.

Radiation therapy alone for stage I (UICC T1N0M0) squamous cell carcinoma of the esophagus: Indications for surgery or combined chemoradiotherapy

The aim of this study was to clarify the efficacy and limitations of radiation therapy (RT) for superficial esophageal carcinoma, and to explore the indications for more aggressive therapy, such as combined chemo-radiotherapy. Sixty-eight patients with stage I (UICC T1N0M0) esophageal squamous cell carcinoma treated by definitive RT alone were analyzed. Brachytherapy was administered in 36 patients as a boost, and the prescribed doses were 10 Gy (5 Gy x 2 times) at a low dose rate (19 patients) and 9 Gy (3 Gy x 3 times) at a high dose rate (17 patients). Recurrence patterns and survival rates were assessed and the factors predisposing to recurrences after RT were statistically investigated by univariate analysis. The 5-year cause-specific survival rate and the locoregional control rate were 79.9% and 82.1%, respectively. No case of recurrence or disease-related death was observed in any of the patients with mucosal cancer. Among the cases with the cancer invading the submucosa, there were 12 cases with locoregional recurrence and two cases with distant metastases. In cases of submucosal esophageal cancer, the tumor length was the only statistically significant factor predicting locoregional control. The 5-year locoregional control rate in cases with a short length of the tumor (<or=5 cm) was 83.3%, whereas the corresponding rate in cases with the tumor measuring >5 cm in length was 57.8% (P = 0.036). Patients treated by additional brachytherapy exhibited better cause-specific survival and locoregional control rates than those receiving external RT alone, however, the addition had no statistically significant influence on the outcome. RT was a successful treatment for stage I esophageal cancer, and the treatment outcome using RT was nearly comparable to that of surgery. However, it is suggested that chemo-radiation should be considered in inoperable cases of submucosal cancer when the tumor is more than 5 cm in length.

Hyperfractionated-Accelerated Radiotherapy Followed by Radical Surgery in Locally Advanced Tumors of the Oral Cavity

To evaluate the outcome of hyperfractionated-accelerated radiotherapy and subsequent planned primary tumor resection and radical neck dissection in locally advanced tumors of the oral cavity. This retrospective analysis evaluates 126 subsequent patients who were treated between 1988 and 1997 for locally advanced tumors of the oral cavity (with extension into the oropharynx in 17 patients), 34 (27%) AJCC stage III and 92 (73%) stage IV. Primary tumor and nodal metastases were irradiated with 1.4 Gy bid to a median total dose of 72.8 Gy (range 58.8-75.6 Gy). Then, planned radical surgery of the primary site according to the initial tumor extent and cervical nodes was performed. Median follow-up of living patients was 6 years (range 1-11 years). 4 weeks after radiotherapy, 14 patients (11%) had complete tumor remission, 92 (73%) partial remission, 15 (12%) no change, and five (4%) progressive disease. Complete resection was achieved in 117 (93%) patients (nine incomplete resections). 5-year locoregional control rate was 62 +/- 9%, overall survival 36 +/- 9%. Surgery-related morbidity occurred in 42 patients (33%; mainly delayed wound healing and fistulae), overall severe treatment-related morbidity in 46 patients (36%). 24/84 relapse-free patients (29%) required a percutaneous gastrostomy or nasal tube > or = 1 year after therapy. In this study, the outcome of combined curative radiotherapy and planned surgery of the primary tumor and neck nodes was comparable to reported results of hyperfractionated radiotherapy with or without salvage surgery of the neck nodes with respect to locoregional control and overall survival. Planned surgery carries a substantial risk of morbidity and seems to offer no benefit in comparison to salvage surgery of the neck nodes only. Therefore, salvage surgery is preferred.

Safety and feasibility of breast conserving therapy in Indian women: Two decades of experience at Tata Memorial Hospital

The NIH consensus statement on the management of breast cancer has highlighted the paucity of outcome data in non-Caucasian women. Treatment outcome and factors determining it in a large cohort of ethnic Indian women treated with breast conserving therapy (BCT) at Tata Memorial Hospital are reported here. During 1980-2000, 1,022 pathological Stage I/II breast cancer patients (median age 43 years) underwent BCT (wide excision, complete axillary clearance, whole breast radiotherapy with 6 MV photons plus tumor bed boost, +/-systemic therapy). Median pathological tumor size was 3 cm (1-5 cm). Axillary node metastases were found in 39% women. Of the 938 patients with IDC, 70% were Grade III and in patients where receptor status was known, 209/625 (33%) were ER positive and 245/591 (41%) were PR positive. The 5- and 10-year actuarial overall survival was 87% and 77% and disease-free survival was 76% and 68%, respectively. Actuarial 5-year local and locoregional control rates were 91% and 87%, respectively. Cosmesis was good or excellent in 78% women. Independent adverse prognostic factors for local recurrence were, age<40 years, axillary node metastasis, lymphovascular invasion (LVI), and adjuvant systemic therapy; for locoregional recurrence-inner quadrant tumor, axillary node metastasis, and LVI; for survival-LVI and axillary node metastasis. Compared to Caucasians, these Indian women undergoing BCT were younger, had larger, higher grade, and receptor negative tumors. Comparable local control and survival was obtained by using stringent quality assurance in the diagnostic and therapeutic protocol. BCT, a resource intense treatment is safe for selected and motivated patients undergoing treatment at centers with adequate facilities and expertise even in countries with limited resources.

Squamous cell carcinoma of the buccal mucosa: An aggressive cancer requiring multimodality treatment

In our clinical practice, we have observed a high incidence of locoregional failure in squamous cell carcinoma (SCC) of the buccal mucosa. We analyze our treatment results of this cancer and compare these results with those in the literature. We intend to define the pattern and incidence of failure of buccal cancer and provide information for the design of a better multimodality treatment. During the period from 1983 through 2003, 121 previously untreated patients with M0 stage SCC of the buccal mucosa were treated with a curative intent at our hospital. Twenty-seven patients received surgery alone, 36 had radiotherapy alone, and 58 underwent surgery plus postoperative radiotherapy. The 5-year locoregional control, overall survival, and cause-specific survival rates for all patients were 36.3%, 34.3%, and 36.9%, respectively. The locoregional recurrence rate was 57% for all patients, with 80% occurring in the primary site alone. Patients with T1-2N0 disease who received surgery alone still had a high local recurrence incidence of 41%. For patients with locally advanced disease, surgery plus postoperative radiotherapy achieved better overall survival and locoregional control rates than surgery alone or radiotherapy alone. T classification was the only prognostic factor affecting locoregional control and survival in the surgery alone group, whereas N classification and skin invasion predicted a poorer survival for the surgery plus postoperative radiotherapy group. SCC of the buccal mucosa is an aggressive cancer with a high locoregional failure rate even in patients with T1-2N0 disease. Possible reasons include inadequate treatment and an intrinsically aggressive nature. Postoperative radiotherapy has resulted in a better locoregional control rate for patients with T3-4 or N+ disease and should also be considered for patients with T1-2N0 disease for whom adjuvant therapy after radical surgery currently is not recommended by most guidelines.

Toxicity and Survival Results of a Phase II Study Investigating the Role of Postoperative Chemo-radioimmunotherapy for Gastric Adenocarcinoma

To investigate the role of postoperative concomitant chemo-radioimmunotherapy in gastric adenocarcinoma patients. 59 patients, who underwent total or subtotal gastrectomy, with lymph node involvement, positive microscopic surgical margins or serosal involvement were included in the study. Radiotherapy started concomitantly with chemotherapy and levamisole. Extended-field radiotherapy was given to gastric bed and regional lymphatics via two anterior-posterior/posterior-anterior fields. A total dose of 45 Gy in 25 fractions with a fraction size of 1.8 Gy was planned. In 28 patients (48%) with positive surgical margins a 10-Gy boost dose was given to the anastomosis site. An adjuvant i.v. bolus of 450 mg/m(2)/day 5-fluorouracil (5-FU) was administered concomitantly during the first 3 days and at the 20th day of irradiation. After completion of radiotherapy, i.v. boluses of 450 mg/m(2)/day 5-FU and 25 mg/m(2)/day rescuvorin were continued for 6 months once a week. Levamisole 40 mg/day orally was started at the 1st day of radiotherapy and also continued for 6 months. Median follow-up was 37 months (7-112 months). Median survival was 23 months. Overall 3- and 5-year survival rates amounted to 35% and 14%, respectively. Median survival of the patients with positive surgical margins was 22 months. The 3- and 5-year locoregional control rates were 59% and 55%, respectively. The most common toxicity was upper gastrointestinal system toxicity, which was observed in 42 patients (71%). Four patients (7%) died on account of early toxic effects, and six (10%) could not complete treatment. Although 48% of the study population involved patients with microscopic residual disease, the survival results as a whole were satisfactory. However, due to high toxicity, radiotherapy must be delivered with the most proper techniques along with adequate nutrition and supportive care.

Adjuvant radiotherapy after transoral laser microsurgery for advanced squamous carcinoma of the head and neck

To evaluate the efficacy of an adjuvant radiotherapy after transoral laser microsurgery for advanced squamous cell carcinoma of the head and neck and to show that a less invasive surgery with organ preservation in combination with radiotherapy is an alternative to a radical treatment. Between 1987 and 2000, 208 patients with advanced squamous cell carcinoma of the head and neck were treated with postoperative radiotherapy after surgical CO2 laser resection. Primary sites included oral cavity, 38; oropharynx, 88; larynx, 36; hypopharynx, 46. Disease stages were as follows: Stage III, 40 patients; Stage IV, 168 patients. Before 1994, the treatment consisted of a split-course radiotherapy with carboplatinum (Treatment A). After 1994, the patients received a conventional radiotherapy (Treatment B). Patients had 5-year locoregional control and disease-specific survival (DSS) rates of 68% and 48%, respectively. The 5-year DSS was 70% and 44% for Stages III and IV, respectively (p = 0.00127). Patients treated with a hemoglobin level greater or equal to 13.5 g/dL before radiotherapy had a 5-year DSS of 55% as compared with 39% for patients treated with a hemoglobin level greater than 13.5 g/dL (p = 0.0054). In this series of patients with advanced head-and-neck tumors, transoral laser surgery in combination with adjuvant radiotherapy resulted in locoregional control and DSS rates similar to those reported for radical surgery followed by radiotherapy. Treatment B has clearly been superior to Treatment A. A further improvement of our treatment regimen might be expected by the combination of adjuvant radiotherapy with concomitant platinum-based chemotherapy.

Risk‐group definition by recursive partitioning analysis of patients with squamous cell head and neck carcinoma treated with surgery and postoperative radiotherapy

The objective of this study was to define different prognostic groups with regard to locoregional control (LRC) derived from recursive partitioning analysis (RPA). Eight hundred one patients with squamous cell head and neck carcinoma underwent with primary surgery and received postoperative radiotherapy. For the definition of prognostic groups, the method of classification and regression trees was performed, including a large number of well known prognostic factors. The final model was composed of six prognostic factors for LRC, resulting in seven terminal nodes. RPA Class I (intermediate risk) consisted of 381 patients who had no N3 lymph nodes, free surgical margins (> 5 mm), and no extranodal spread (ENS). RPA Class II (high risk) consisted of 189 patients who had 1 positive lymph node with ENS or had T1, T2, or T4 tumors with close or positive surgical margins. RPA Class III (very high risk) consisted of 231 patients who had a N3 neck, > or = 2 positive lymph nodes with ENS, or a T3 tumor with close or positive surgical margins. The 5-year LRC rate was 88%, 73% and 58%, in RPA Class I, II, and III, respectively (P < 0.0001). The hazard ratio (HR) relative to RPA Class I was 2.3 (95% confidence interval [95%CI], 1.5-3.6) for RPA Class II and 4.2 (95%CI, 2.8-6.1) for RPA Class III. The RPA classification scheme studied allowed for the clear definition of three prognostic groups with regard to LRC and OS. These groups may be useful in the design of future prospective, randomized studies investigating new treatment modalities.

Expressions of Ku70 and DNA-PKcs as prognostic indicators of local control in nasopharyngeal carcinoma

The objective of this study was to determine whether the expressions of the two components of DNA-dependent protein kinase, Ku70 and DNA-protein kinase catalytic subunit (DNA-PKcs), influence the response to radiotherapy (RT) and outcome of treatment of nondisseminated nasopharyngeal carcinoma (NPC) in patients who received definitive RT. Sixty-six patients with NPC who were treated with radiotherapy alone or with concurrent chemotherapy between June 1995 and December 2001 were divided into groups based on the levels of immunoreactivity for Ku70 and DNA-PKcs in pretreatment biopsy specimens. The overexpression of Ku70 or DNA-PKcs groups included patients whose biopsy specimens showed at least 50% immunopositive tumor cells; patients in which less than 50% of the tumor cells in the biopsy tissues were immunopositive were placed in the low Ku70 and DNA-PKcs groups. The immunoreactivities for Ku70 and DNA-PKcs were retrospectively compared with the sensitivity of the tumor to radiation and the patterns of therapy failure. Univariate analyses were performed to determine the prognostic factors that influenced locoregional control of NPC. The 5-year locoregional control rate was significantly higher in the low Ku70 group (Ku-) (85%) than in the high Ku70 group (Ku+) (42%) (p = 0.0042). However, there were no differences in the metastases-free survival rates between the 2 groups (Ku70+, 82%; Ku70- 78%; p = 0.8672). Univariate analysis indicated that the overexpression of Ku70 surpassed other well-known predictive clinicopathologic parameters as an independent prognostic factor for locoregional control. Eighteen of 22 patients who had locoregional recurrences of the tumor displayed an overexpression of Ku70. No significant association was found between the level of DNA-PKcs expression and the clinical outcome. Our data suggest that the level of Ku70 expression can be used as a molecular marker to predict the response to RT and the locoregional control after RT and concurrent chemotherapy in patients with nondisseminated NPC.

Retromolar Trigone Carcinoma Treated by Primary Radiation Therapy

To review our experience in the treatment of retromolar trigone carcinoma with radiotherapy as the primary modality and to evaluate the different factors affecting locoregional control and survival. We retrospectively examined 46 patients with squamous cell carcinoma of the retromolar trigone treated primarily with radiotherapy from January 1, 1973, to June 31, 2002. Four had T1, 21 had T2, 17 had T3, and 4 had T4 lesions; 25 had N0, 15 had N1, 5 had N2, and 1 had N3 disease. The overall stage was I in 3, II in 18, III in 18, and IV in 7 patients. All patients received conventional once-daily fraction radiotherapy as the primary modality of treatment. Three patients received chemotherapy. Overall survival, cause-specific survival, and locoregional control were estimated using the Kaplan-Meier method. Log-rank statistics were used to identify significant prognostic factors for overall survival and locoregional control. The median follow-up was 43 (range, 5-217) months overall and 78 (range, 26-188) months for living patients. The 5-year overall survival and cause-specific survival rates were 47% and 78%, respectively. Favorable prognostic factors for cause-specific survival were a lower tumor stage (univariate and multivariate analysis) and a lower nodal stage (multivariate analysis). The 5-year local control rate was 49% after radiotherapy and 67% after salvage surgery. The 5-year regional control rate was 88%. Favorable prognostic factors were a lower nodal stage and a lower overall stage (univariate analysis). The 5-year locoregional control rate for all patients was 42% after radiotherapy and 70% after salvage surgery. Given the surgical salvage rate in our series and previous published experience, radiation therapy can be used with curative intent for small retromolar trigone carcinomas (T1-T2 lesions). For advanced stages without bone invasion, consideration for concurrent chemotherapy and radiation therapy might increase previous historical locoregional and survival rates.

Radiotherapy alone or combined with surgery for salivary gland carcinoma

The authors analyzed the outcomes of patients treated with radiotherapy (RT) alone or combined with surgery for carcinoma of the salivary glands. Between October 1964 and June 2003, 224 previously untreated patients were treated with curative intent with RT alone (n = 64) or combined with surgery (n = 160) at the University of Florida College of Medicine (Gainesville, FL). The median follow-up period was 5.0 years (range, 0.4-31.6 years). The 10-year local control rate was 75%. Multivariate analysis of local control revealed that T classification (P < 0.0001) and treatment group (P < 0.0001) impacted this end point. Patients treated with surgery and adjuvant RT had improved local control compared with patients treated with RT alone. The 10-year locoregional control rate was 68%. Multivariate analysis of locoregional control revealed that overall stage (P < 0.0001) and treatment group (P = 0.0002) significantly influenced this end point. The 10-year distant metastasis-free survival rate was 68%. Multivariate analysis of distant metastasis-free survival revealed that overall stage (P < 0.0001) significantly influenced this end point. The 10-year cause-specific and overall survival rates were 57% and 44%, respectively. Multivariate analysis of cause-specific survival revealed that overall stage (P < 0.0001) significantly impacted this end point. Twenty-three patients (10%) experienced severe complications. A substantial proportion of patients with salivary gland carcinoma were cured with surgery combined with adjuvant RT. RT alone was used for patients with unresectable tumors and cured approximately 20% of those with advanced-stage disease. The probability of cure was influenced by the extent of disease and treatment group.

Proton radiation for treatment of cancer of the oropharynx: Early experience at Loma Linda University Medical Center using a concomitant boost technique

To assess accelerated fractionation using photon and proton radiation to improve local control and reduce complications in treating locally advanced oropharyngeal cancer. Twenty-nine patients with localized Stage II-IV oropharyngeal cancer received accelerated photon and proton radiation, 75.9 GyE in 45 fractions/5.5 weeks, to the primary disease, involved lymph nodes, and potential areas of subclinical spread. Follow-up ranged from 2 to 96 months. Five-year actuarial control for local disease was 88%, and for neck node disease, 96%; yielding a 84% locoregional control rate at 5 years. Four patients developed distant metastases. The 5-year actuarial locoregional control rate was 84%. The actuarial 2-year disease-free survival rate was 81%; at 5 years, it was 65%. All patients completed the prescribed treatment; though aggressive nutritional and anesthetic support was necessary. Late Grade 3 toxicity was seen in 3 patients. Protons used as a concomitant boost with photons effectively delivered an accelerated time-dose schedule to the cancer with a more tolerable schedule to surrounding normal tissues. Preliminary results reveal increased locoregional control without increased toxicity. Future studies must evaluate the optimum time-dose schedule.

Twice-daily reirradiation for recurrent and second primary head-and-neck cancer with gemcitabine, paclitaxel, and 5-fluorouracil chemotherapy

We previously demonstrated the efficacy of concurrent gemcitabine, paclitaxel, and 5-fluorouracil in conjunction with twice-daily (1.5-Gy) radiotherapy delivered on alternating weeks (TFGX(2)) in locally advanced head-and-neck cancer. Here, we report the clinical outcome and late toxicity of TFGX(2) in a subset of patients previously irradiated to the head and neck. Twenty-nine previously irradiated patients, presenting with recurrent or second primary head-and-neck cancer, underwent TFGX(2). Twelve patients underwent attempted surgical resection before chemoradiotherapy, 10 of whom were left with no measurable disease. Patients with measurable disease received a median radiation dose of 72 Gy; those with no measurable disease received a median dose of 61 Gy. The cumulative dose ranged from 74.4 to 156.4 Gy (mean, 125.7 Gy; median, 131.0 Gy). The median follow-up was 19.1 months (50.9 months for living patients). The 5-year overall survival rate was 34.5%, and the locoregional control rate was 54.5%. In patients with measurable disease at treatment, the 5-year overall survival and locoregional control rate was 26.3% and 45.1%, respectively, compared with 50.0% (p = 0.14) and 70% (p = 0.31), respectively, for those with no measurable disease. Measurable disease and radiation dose were highly statistically significant for overall survival and locoregional control on multivariate analysis. Of 14 patients assessable for late toxicity, 3 developed Grade 4-5, 8 Grade 2-3, and 3 Grade 0-1 toxicity. Aggressive reirradiation with chemotherapy in locally advanced head-and-neck cancer provides a chance for long-term cure at the expense of toxicity. Attempted surgical resection before chemoradiotherapy improved disease control and survival.

Intraoperative 125I Vicryl mesh brachytherapy after sublobar resection for high-risk stage I nonsmall cell lung cancer

Purpose To assess the feasibility and outcomes of 125I Vicryl mesh brachytherapy after sublobar resection in stage I nonsmall cell lung cancer (NSCLC) patients with poor pulmonary function. Methods and materials Between January 1997 and July 2004, patients with poor cardiopulmonary reserve who had stage IA and IB (T1-2 N0 M0) NSCLC and a forced expiratory volume in 1 s (FEV 1) of ≥0.6 L were considered for limited surgical resection either by an open or video-assisted thoracoscopic procedure and for a subsequent 125I Vicryl mesh brachytherapy implant. Mediastinal and hilar lymph node staging was performed routinely in all patients. After clear margins were obtained grossly and on frozen section, a single-plane 125I implant was designed to encompass a plane consisting of the staple line and a 2-cm margin of surrounding visceral pleura. The implant was introduced through the surgical incision and sutured to the visceral pleura. A prescribed dose of 100–120 Gy was delivered to a volume within 0.5 cm from the plane of the implant. Follow-up orthogonal films or CTs were obtained for dosimetric analysis. Kaplan–Meier analyses were used to estimate the local control, locoregional control, and overall survival rates. Results Of the 110 patients, 65 had stage IA and 45 had stage IB NSCLC. The mean preoperative FEV 1 was 47% of the predicted volume. With a median follow-up of 11 months (range 1–68 months), there were four recurrences within the radiation volume. The estimated 5-year local (in-field) control, locoregional control, and overall survival rates were 90%, 61%, and 18%, respectively. Conclusion Vicryl mesh brachytherapy after sublobar resection for high-risk stage I NSCLC patients is a feasible procedure, which results in an excellent local (in-field) control rate.

Esophagectomy after concurrent chemoradiotherapy improves locoregional control in clinical stage II or III esophageal cancer patients

To evaluate the effect of surgical resection on the outcome of patients with clinical Stage II or III cancer of the esophagus treated with concurrent chemoradiotherapy. A retrospective review of 132 consecutive patients with clinical Stage II or III esophageal cancer treated with concurrent chemoradiotherapy between January 1990 and December 1998 was performed. Of the 132 patients, 60 underwent esophagectomy 6-8 weeks after chemoradiotherapy. The median radiation dose was 50 Gy (range, 30-64.8 Gy) in the definitive chemoradiation group and 45 Gy (range, 30-50.4 Gy) in the chemoradiation plus esophagectomy group. Statistically significant differences were found between the two groups in median age, histologic subtype, tumor location, and number of patients with T4 disease. Patients who underwent definitive chemoradiotherapy were older (p = 0.0004) and more likely to have squamous cell carcinoma than adenocarcinoma (p <0.000), upper thoracic or cervical esophageal tumors (p <0.000), and T4 tumors (p = 0.024). Patients treated with chemoradiation plus esophagectomy had statistically significant superior 5-year loco-regional control (67.1% vs. 22.1%, p <0.000), disease-free survival (40.7% vs. 9.9%, p < 0.000), and 5-year overall survival (52.6% vs. 6.5%, p < 0.000) rates and median survival time (62 vs. 12 months) compared with patients treated with chemoradiotherapy only. However, no statistically significant difference was found in the rate of distant metastasis-free survival between the two groups (67.5% vs. 65.8%, p = 0.3). Surgical resection of the tumor was an independent predictor of improved locoregional control and overall survival in both univariate and multivariate analyses. To reduce the effect of the selection bias on the outcome, 34 patients in each group with matched pretreatment characteristics were compared. The results showed statistically significant better overall survival, disease-free survival, and locoregional control in favor of the chemoradiotherapy plus esophagectomy group. No statistically significant difference in distant metastasis-free survival was found in this subgroup analysis. Locoregional control was better in clinical Stage II or III esophageal cancer patients treated with concurrent chemoradiation plus esophagectomy. An improvement in survival occurred in the chemoradiation plus esophagectomy group, although this observation may have reflected selection bias. The results from this study suggest the need for a randomized trial to compare chemoradiation with or without esophagectomy in the treatment of cancer of the esophagus.

Postoperative irradiation for squamous cell carcinoma of the oral cavity: 35-year experience.

The purpose of this study was to analyze factors influencing outcome in patients who received postoperative irradiation for advanced squamous cell carcinoma of the oral cavity. Between October 1964 and November 2000, 226 patients with 230 previously untreated primary invasive squamous cell carcinomas of the oral cavity were treated postoperatively with continuous-course external beam irradiation. All patients had a minimum follow-up of 2 years (analysis, November 2002). No patient was lost to follow-up. The 5-year actuarial rates of locoregional control by pathologic American Joint Committee on Cancer stage were: stage I, 100%; stage II, 84%; stage III, 78%; and stage IV, 66%. Recurrence of cancer above the clavicles developed in 55 patients (24%). In multivariate analysis of locoregional control, positive margins, vascular invasion, perineural invasion, extracapsular extension, and T classification remained significant. This article provides additional data defining relatively favorable and unfavorable groups of patients in the postoperative setting. Dose recommendations are re-examined and selectively increased for high-risk patients.

Induction chemotherapy improved outcomes of patients with resectable esophageal cancer who received chemoradiotherapy followed by surgery

Purpose To investigate the effect of induction chemotherapy (CHT) before trimodality therapy on the outcome of patients with resectable cancer of the esophagus. Methods and materials This retrospective study included 81 consecutive patients with resectable cancer of the esophagus who received neoadjuvant chemoradiotherapy followed by esophagectomy between January 1990 and December 1998 (inclusive). Thirty-nine patients underwent chemoradiotherapy followed by esophagectomy (CHT/RT+S), 42 received additional induction CHT followed by CHT/RT+S (CHT+CHT/RT+S). Of the 81 patients, 47 were entered in institutional or national prospective trials (6 in the CHT/RT+S and 41 in the CHT+CHT/RT+S group). Induction CHT consisted of three courses of 5-fluorouracil (5-FU), cisplatin, and paclitaxel given in 28-day cycles in 37 patients (88.1%). Concurrent CHT was 5-FU and platinum based. The median radiation dose for patients treated with CHT/RT+S was 30 Gy (range, 30–50.4 Gy) delivered in a median of 10 fractions (range, 10–28 fractions) and 45 Gy (range, 30–45 Gy) in a median of 25 fractions (range, 10–25 fractions) for patients treated with CHT+CHT/RT+S. Esophagectomy was performed 6–8 weeks after completion of concurrent chemoradiotherapy. Most patients underwent transthoracic esophagectomy ( n = 66, 82.5%). Results The pretreatment characteristics were well balanced between the two groups except for age. The median follow-up time was 29 months (22 months for the CHT/RT+S group and 38.5 months for the CHT+CHT/RT+S group) for all patients and 49 months for living patients. The actuarial overall survival (OS), disease-free survival (DFS), locoregional control (LRC), and distant metastasis-free survival (DMFS) rate at 5 years for the entire group was 46%, 36.6%, 70.7%, and 53.2%, respectively. Statistically significant differences in the OS, DFS, and LRC rates between the two groups were detected. Specifically, the 5-year OS rate was 22.8% and 71.1% in the CHT/RT+S and CHT+CHT/RT+S group ( p = 0.0001), respectively. The 5-year DFS rate was 27.6% and 56.6% in the CHT/RT+S and CHT+CHT/RT+S group ( p = 0.003), respectively. The 5-year LRC rate was 64.2% and 85.6% in the CHT/RT+S and CHT+CHT/RT+S group ( p = 0.007), respectively. The difference in the DMFS rate between the two groups was statistically significant, with a 2- and 5-year actuarial rate of 63.9% and 51.9%, respectively, in the CHT/RT+S group and 76.9% and 74.1%, respectively, in the CHT+CHT/RT+S group ( p = 0.04). The statistically significant differences persisted when patients who received ≥45 Gy in each group were compared. Among those patients, the 5-year OS, DFS, LRC, and DMFS rates were 23.1%, 15.4%, 58.6%, and 39.2%, respectively, for those receiving CHT/RT+S, and 71.4% ( p = 0.001), 55.8% ( p = 0.0008), 84.6% ( p = 0.005), and 77.3% ( p = 0.009), respectively, for those receiving CHT+CHT/RT+S. The pathologic complete response (pCR) rate was greater in the CHT+CHT/RT+S group compared with in the CHT/RT+S group ( p = 0.008). In univariate analysis, young age, good Karnofsky performance status, Stage II disease, total radiation dose, multiple drug regimen for concurrent CHT, pCR, R0 resection, distant disease progression, and CHT+CHT/RT+S treatment proved to be prognostic factors for OS. Lower esophageal/gastroesophageal junction tumor location, pCR, R0 resection, and CHT+CHT/RT+S treatment were favorable prognostic factors for LRC. Neither the total radiation dose nor multiple drugs for concurrent CHT were negative prognostic factors for LRC. In multivariate analysis, pCR, R0 resection, and treatment with CHT+CHT/RT+S were independent positive predictive factors for OS, and distant recurrences were negative predictive factors for OS. R0 resection, CHT+CHT/RT+S treatment, and lower esophageal/gastroesophageal junction tumor location were positive predictive factors for LRC. The radiation dose was not identified as an independent prognostic factor for either OS or LRC in the multivariate analysis. Meaningful multivariate analysis could not be performed when the multiple drug variable was included in the model because of the small number of patients. Conclusion Significantly greater LRC, DFS, OS, and DMFS were found in patients treated with CHT+CHT/RT+S compared with those treated with CHT/RT+S. The pCR rate was significantly higher in the CHT+CHT/RT+S group. Induction CHT was an independent favorable prognostic factor for both LRC and OS for the population included in this study. Our data suggest that a randomized trial comparing CHT+CHT/RT+S and CHT/RT+S is warranted to assess further the merits of this treatment in patients with this currently very lethal cancer.

Adjuvant radiotherapy after transoral microlasersurgery for advanced primary squamous cell carcinoma of the head and neck

We are presenting a retrospective analysis which is the first publication worldwide, focusing on adjuvant radiotherapy after laser surgery for advanced head and neck cancer based on a major case load. The treatment outcome is presented for a total of 208 patients treated at a single institution. The main advantage of laser surgery is the maintenance of organ function. In term of local control, survival, and quality of life the study compares favourably with the published reports on multimodal treatment in advanced head and neck cancer. Evaluation of risk factors revealed tumour stage, hemoglobin concentration at initiation of treatment, and the technique of adjuvant radiotherapy as major prognostic factors for therapeutic outcome. Between 1987 and 2000, 208 patients with advanced SCC of the head and neck were treated at the university of Goettingen (Germany), with postoperative RT following surgical CO2 laser-resection. Primary sites included oral cavity, 38; oropharynx, 88; larynx, 36; hypopharynx, 46. Disease stages were as follows: St. III, 40 patients, St. IV, 168 patients. The postoperative nodal stage was: pN0, 37 patients; pN1, 35 patients; pN2, 117 patients; and pN3, 19 patients. The radiotherapy protocol changed over time at our institution. Before 1994, the treatment A consisted of two fractions per day (2x 2.1 Gy), preceded by a dose of 50 mg/m2 carboplatinum i.v. daily. A total radiation dose of 56.70 Gy was applied to the neck and the primary tumour over 6 weeks as a split course regimen with a brake of 2 weeks. After 1994, treatment B consisted of a conventional radiotherapy (50 Gy + 10 Gy Boost) delivered in 30 treatment fractions of 2.0 Gy. Follow-up: All patients were examined every 6 months during the first 3 years after therapy, and every year after this period. They underwent clinical ENT-examination including magnifying laryngososcopy, ultrasound, and/or a computed tomography of the head and neck region if indicated. Statistics: Survival and local-regional control probabilities were calculated from the day of surgery. Disease Free Survival (DFS) was defined as the absence of recurrent disease above the clavicles and the absence of distant metastases. The Kaplan-Meier product-limit method was used to determine survival and the time to local failure. The log rank method was used to test for statistical significance. Multivariate analyses were estimated by means of the Cox proportional hazards model. Follow-up data were available on all patients. Each of them was followed until death for those who died or until December 2001 for those who were alive. The median follow-up period was 75 months (range 31 to 137 months). The Disease Specific Survival (DSS) and the Locoregional Control (LRC) were estimated with the Kaplan Meier curves. Patients had 5-year locoregional control (LRC) and diseases specific survival (DSS) rates of 62.5 %, and 45 %, respectively. The 5-year DSS was 66 % and 38 % for the stage III and IV, respectively (p = 0.006). Patients treated with a hemoglobin level superior or equal to 13.5 g/dl before radiotherapy had a 5-year DSS of 48.5% as compared with 37 % for patients treated with a hemoglobin level inferior to 13.5 g/dl (p = 0.01). The largest difference was found between the patients who received treatment B and who had a hemoglobin level superior or equal to 13.5 g/dl before radiotherapy and the patients who received treatment A who had a hemoglobin level inferior to 13.5 g/dl. In the first group the 5-year DSS was 54% compared with 38% in the second group (p = 0.002). In this series of patients with advanced head and neck tumours transoral laser surgery in combination with adjuvant radiotherapy resulted in locoregional control and DSS rates similar to those reported for radical surgery followed by radiotherapy. Laser surgery apparently leaves patients in a better clinical condition with higher hemoglobin levels and reduced surgical trauma, which is both likely enhancing the efficacy of postoperative radiotherapy

Adjuvant radiotherapy after transoral microlasersurgery for advanced primary squamous cell carcinoma of the head and neck

We are presenting a retrospective analysis which is the first publication worldwide, focusing on adjuvant radiotherapy after laser surgery for advanced head and neck cancer based on a major case load. The treatment outcome is presented for a total of 208 patients treated at a single institution. The main advantage of laser surgery is the maintenance of organ function. In term of local control, survival, and quality of life the study compares favourably with the published reports on multimodal treatment in advanced head and neck cancer. Evaluation of risk factors revealed tumour stage, hemoglobin concentration at initiation of treatment, and the technique of adjuvant radiotherapy as major prognostic factors for therapeutic outcome. Between 1987 and 2000, 208 patients with advanced SCC of the head and neck were treated at the university of Goettingen (Germany), with postoperative RT following surgical CO2 laser-resection. Primary sites included oral cavity, 38; oropharynx, 88; larynx, 36; hypopharynx, 46. Disease stages were as follows: St. III, 40 patients, St. IV, 168 patients. The postoperative nodal stage was: pN0, 37 patients; pN1, 35 patients; pN2, 117 patients; and pN3, 19 patients. The radiotherapy protocol changed over time at our institution. Before 1994, the treatment A consisted of two fractions per day (2x 2.1 Gy), preceded by a dose of 50 mg/m2 carboplatinum i.v. daily. A total radiation dose of 56.70 Gy was applied to the neck and the primary tumour over 6 weeks as a split course regimen with a brake of 2 weeks. After 1994, treatment B consisted of a conventional radiotherapy (50 Gy + 10 Gy Boost) delivered in 30 treatment fractions of 2.0 Gy. Follow-up: All patients were examined every 6 months during the first 3 years after therapy, and every year after this period. They underwent clinical ENT-examination including magnifying laryngososcopy, ultrasound, and/or a computed tomography of the head and neck region if indicated. Statistics: Survival and local-regional control probabilities were calculated from the day of surgery. Disease Free Survival (DFS) was defined as the absence of recurrent disease above the clavicles and the absence of distant metastases. The Kaplan-Meier product-limit method was used to determine survival and the time to local failure. The log rank method was used to test for statistical significance. Multivariate analyses were estimated by means of the Cox proportional hazards model. Follow-up data were available on all patients. Each of them was followed until death for those who died or until December 2001 for those who were alive. The median follow-up period was 75 months (range 31 to 137 months). The Disease Specific Survival (DSS) and the Locoregional Control (LRC) were estimated with the Kaplan Meier curves. Patients had 5-year locoregional control (LRC) and diseases specific survival (DSS) rates of 62.5 %, and 45 %, respectively. The 5-year DSS was 66 % and 38 % for the stage III and IV, respectively (p = 0.006). Patients treated with a hemoglobin level superior or equal to 13.5 g/dl before radiotherapy had a 5-year DSS of 48.5% as compared with 37 % for patients treated with a hemoglobin level inferior to 13.5 g/dl (p = 0.01). The largest difference was found between the patients who received treatment B and who had a hemoglobin level superior or equal to 13.5 g/dl before radiotherapy and the patients who received treatment A who had a hemoglobin level inferior to 13.5 g/dl. In the first group the 5-year DSS was 54% compared with 38% in the second group (p = 0.002). In this series of patients with advanced head and neck tumours transoral laser surgery in combination with adjuvant radiotherapy resulted in locoregional control and DSS rates similar to those reported for radical surgery followed by radiotherapy. Laser surgery apparently leaves patients in a better clinical condition with higher hemoglobin levels and reduced surgical trauma, which is both likely enhancing the efficacy of postoperative radiotherapy

Radiation therapy for early-stage carcinoma of the oropharynx

Purpose To evaluate the outcomes of radiation therapy treatment of patients with Stage I and II squamous cell carcinoma (SCC) of the oropharynx and discover adverse prognostic factors that may help select a subgroup of patients for a different management approach. Methods and materials A search of the database maintained by the Department of Radiation Oncology of The University of Texas M. D. Anderson Cancer Center for patients with Stage I or II SCC of the oropharynx was performed. This search identified 175 patients treated between 1970 and 1998 who met the inclusion criteria for this retrospective study. Distribution of primary sites was: tonsillar fossa/pillar, 60 patients; soft palate, 55 patients; base of tongue, 40 patients; and pharyngeal wall, 20 patients. Twenty-five patients were stage T1, 124 were T2, and 26 were Tx. All patients were treated with fractionated radiation to a median dose of 66 Gy. Eighty-five patients were treated with conventionally fractionated radiation, 73 were treated with the concomitant boost fractionation schedule, and the remaining 17 were treated with other altered fractionation schedules or with intraoral or interstitial boosts. Results The median follow-up for all patients was 76 months (range, 2–302 months). The actuarial 5-year local control (LC), regional control, locoregional control (LRC), and disease-free survival (DFS) rates were 85%, 93%, 81%, and 77%, respectively. Only 7 patients (5%) with LC developed nodal metastases, and 10 patients (7%) with LRC developed distant metastases. Eleven patients (32%) with locoregional recurrence were rendered without evidence of disease after a surgical salvage procedure, resulting in a 5- year ultimate LRC rate of 87%. T-stage classification was statistically significant ( p = 0.03) in univariate analysis for actuarial 5-year LRC, 88% for Stage I vs. 72% for Stage II. The 5- and 10-year disease-specific survival rates were 85% and 79%, respectively, while the actuarial 5- and 10-year overall survival rates were 70% and 43%, respectively. Fifty-one patients (29%) developed second primary tumors, 86% of which were cancers of the upper aerodigestive tract (UADT). Heavy alcohol consumption was associated with both an increased risk of disease recurrence and development of a second cancer of the UADT. Conclusions Patients with early-stage oropharynx cancer have high rates of disease control when treated with radiation. Lymphatic and hematogenous metastases are uncommon. Surgical salvage of disease recurrence is successful in approximately one-third of patients. As the majority of recurrences occur within the first 2 years from treatment, close observation during this time period is important. The development of second primary tumors of the UADT adversely impacts survival in these patients to as great a degree as the index cancer.