External-beam radiotherapy in T1-2 N0 penile carcinoma

AimsTo review the outcome of 41 patients with invasive carcinoma of the penis treated with external-beam radiotherapy using a consistent technique and dose.Materials and methodsForty-one patients with carcinoma of the penis treated at Christie Hospital, Manchester, UK, between 1995 and 2000 were reviewed retrospectively. Radiotherapy was delivered using 4 MV linear accelerators with a dose of 50 Gy or 52.5 Gy in 16 fractions over 22 days.ResultsThe distribution of patients according to stage was T1 = 37, T2 = 4, N0 = 40, N3 = 1. Median follow-up was 4.5 years. The local control rate was 62%, nodal relapse-free rate of 88%, relapse-free rate of 51% and overall survival of 88% at 5 years. All recurrences were salvaged by surgery. Penile ulceration occurred in 8% and urethral stenosis requiring dilatation in 29%. There were no penectomies for penile necrosis.ConclusionEBXRT may be offered for T1-2 cancer of the penis with close surveillance to detect local recurrences early for salvage surgery without jeopardising overall survival. It remains an alternative option to penis-preserving surgery and should be discussed in a multidisciplinary setting and with the patient.     

Iridium 192 implantation of T1 and T2 carcinomas of the mobile tongue

Between 1970 and 1986, 166 patients with T1 or T2 epidermoid carcinomas of the mobile tongue were treated by iridium 192 implantation (70 T1N0, 83 T2N0, 13 T1-2 N1-3). Five-year actuarial survival was 52% for T1N0, 44% for T2aN0, and 8% for or T1-2 N1-3. Cause specific survivals were 90%, 71%, and 46%, respectively. Local control was 87% for both T1N0 and T2N0, and 69% for T1-2 N1-3. Seven of 23 failures were salvaged by surgery, increasing local control to 96% for T1 and 90% for T2. Thirty-six patients developed a minor or moderate necrosis (16% T1, 28% T2). Half of these involved bone but only five required surgical intervention. Both local control (LC) and necrosis (nec) increased with increasing dose but improvement beyond 65 Gy is minimal (less than or equal to 60 Gy: LC = 78% nec = 13%; 65 Gy: LC = 90% nec = 29%; greater than or equal to 70 Gy: LC = 94% nec = 23%). For N0 patients, neck management consisted of surveillance (n = 78), elective neck dissection followed with external irradiation for pathologically positive nodes (n = 72), or irradiation (n = 3). Clinically positive nodes (13 patients) were managed by either neck dissection followed by external irradiation if pathologically positive (n = 10) or irradiation alone (n = 3). Regional control was 79% for N0 patients, improving to 88% after surgical salvage, and was 9/13 for N1-3 patients. We recommend that T1 and T2 carcinomas of the mobile tongue be treated by iridium 192 implantation to deliver 65 Gy. Mandibular necrosis should be reduced by using an intra-oral lead-lined dental mold.     

Time-dose-response relationships in postoperatively irradiated patients with head and neck squamous cell carcinomas.

BACKGROUND AND PURPOSE: To define the influence of the dose and time on the response to treatment in postoperatively irradiated head and neck cancer patients and to establish a good prediction of failure. METHODS AND MATERIALS: From January 1985 to December 1995, 214 patients with histologically proven head and neck squamous cell carcinomas were irradiated after radical surgery or single tumour resection according to surgical and histopathological findings. The total doses given ranged between 50 and 75 Gy to the primary bed tumour and between 42 and 56 Gy to the neck with fraction sizes of 1.7-2 Gy/day. The median length of the time interval between surgery and radiotherapy, time of irradiation and total treatment time were 81, 59 and 139 days, respectively. The end-point analyzed was the local-regional tumour control rate at the primary tumour bed and neck for 5 years from the beginning of radiotherapy. Univariate and multivariate analyses were used to determine predictors of failure from among the following studied variables: (i), clinical stage (T/N) of the patients; (ii), tumour grade; (iii), neck surgery; (iv), tumour margins; (v), histological tumour nodal extension; (vi), chemotherapy; (vii), normalized total dose; (viii), time interval between surgery and radiotherapy; (ix), time of irradiation; and (x), total treatment time. RESULTS: The actuarial 5-year tumour control rate for the entire group was 72%, and 92% of the patients who achieved local control are currently alive without disease. Tumour control was inversely related to T stage (83% for T2 vs. 57% for T4) and the probability of local control within each stage was dependent on the N status (> or =71% for T3-T4/N0 vs. 31-44% for T3-T4/N1-N3). Histological N status and tumour margins, but not tumour grade, impacted significantly on tumour control. When local control was analyzed as a function of the dose to the primary, a non-significant negative dose-response relationship was found. The total treatment time was a significant prognostic factor, and the time interval between surgery and irradiation proved to be an independent predictor of failure. CONCLUSIONS: Despite the absence of a statistically significant dose-response relationship, the present results suggest that postoperative irradiation treatment given to patients with head and neck squamous cell carcinomas should not be unduly prolonged, in order to minimize the amount of tumour cell proliferation. In these patients, nodal involvement, positive margins of the resected specimens and time interval between surgery and irradiation were the most important prognostic factors.     

Radiotherapy in T1 laryngeal cancer: prognostic factors for locoregional control and survival, uni- and multivariate analysis

From 1975 through 1985, 194 patients with T1 glottic, 37 patients with T1 supraglottic, and 3 patients with T1 subglottic cancer were treated with radiotherapy. Local control and ultimate locoregional control (after salvage surgery) was 91% and 97% for T1 glottic, 84% and 81% for T1 supraglottic, and 2/3 and 3/3, respectively for subglottic tumors. In uni- and multivariate analysis local control for glottic tumors was associated with extension of the tumor on the vocal cord (entire length of vocal cord vs others, p = 0.01) and continuation of smoking after therapy (yes/no, p = 0.03). No prognostic factor for local control was found in supraglottic tumors. However, regional control and survival were impaired by N stage (N0 vs N+, p less than 0.0005), local recurrence (yes/no, p less than 0.0005), and extension of the tumor (one supraglottic subsite vs more than one, p less than 0.05). Mild late complications were seen in 13% of patients without salvage therapy. Following univariate analysis, field size, fraction size (greater than 2 Gy), maximum tumor dose (greater than 70 Gy), age, post-treatment biopsy, and tumor site were associated with complication rate. Following multivariate analysis, site, fraction size, maximum tumor dose, and continuation of smoking after therapy were independent prognostic factors for mild late complications (mostly arytenoid edema).     

High-dose-rate intracavitary brachytherapy boost for early T stage nasopharyngeal carcinoma{private}

PURPOSE: To investigate any possible therapeutic gain from dose escalation with brachytherapy for early T stage nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: One hundred forty-five patients with T1-2b N0-3 NPC were boosted with high-dose-rate intracavitary brachytherapy after completion of two-dimensional external radiotherapy (ERT) during the period from 1999 to 2003. To compare the efficacy of brachytherapy boost, another 142 patients with T1-2b N0-3 disease who were treated with ERT alone during 1994 to 1999 were evaluated. All patients were treated with ERT to a total dose of 66 Gy in 6.5 weeks. The brachytherapy boost group was given 10-12 Gy in 2 weekly fractions. RESULTS: Dose escalation beyond 66 Gy with brachytherapy boost was shown to improve local control and survival. The 5-year actuarial local failure-free survival, regional failure-free survival, distant metastasis-free survival, progression-free survival, cancer-specific survival, and overall survival rates for the brachytherapy group and the control group were 95.8% and 88.3% (p = 0.020), 96% and 94.6% (p = 0.40), 95% and 83.2% (p = 0.0045), 89.2% and 74.8% (p = 0.0021), 94.5% and 83.4% (p = 0.0058), and 91.1% and 79.6% (p = 0.0062), respectively. The 5-year major-complication-free survival rate was 89.5% for the brachytherapy group and 85.6% for the control group (p = 0.23). CONCLUSIONS: For patients who are treated with two-dimensional treatment techniques, dose escalation with brachytherapy boost improves local control and overall survival of patients with T1-T2a and possibly non-bulky T2b disease.     

Long-term control of T2-T3 rectal adenocarcinoma with radiotherapy alone

PURPOSE: To analyze the long-term result of patients presenting with T2-T3 rectal adenocarcinoma treated with curative intent by radiotherapy (RT) alone, using a combination of contact RT, external beam RT, and brachytherapy with an iridium implant. Patients were considered unsuitable for surgery because of the presence of severe comorbidity or because they did not consent to surgery and the possibility of a permanent stoma. METHODS AND MATERIALS: Between 1986 and 1998, 63 patients (56 staged with endorectal ultrasonography) were entered into a pilot study. Patients had to have T2-T3, N0-N1, M0 adenocarcinoma of the middle or lower rectum involving less than two-thirds of the circumference. RT began with contact X-rays (80 Gy in 3 fractions for 21 days), followed by external beam RT (39 Gy in 13 fractions for 17 days) with a concomitant boost (4 Gy in 4 fractions). After a 4-6-week interval, an iridium implant delivered a completion dose of 20 Gy to the tumor. No chemotherapy was given. RESULTS: The median age of the patients was 72 years. Of the 63 patients, 41 had T2 and 22 had T3 tumors. The mean distance of the tumor from the anal verge was 3.6 cm. All patients completed treatment according to the protocol, except for 7 for whom brachytherapy was not performed. With a median follow-up time of 54 months, the primary local tumor control rate was 63%; after salvage surgery, the ultimate pelvic control was 73% (46 of 63). The 5-year overall survival rate was 64.4%, and for 42 patients aged <80 years, it was 78% with 10 patients alive and well at > or =10 years. No severe Grade 3-4 toxicity was seen. Acute proctitis was seen in most patients but did not require treatment interruption. Late rectal bleeding occurred in 24 patients. Only 1 required blood transfusion. Good anorectal function was maintained in 92% of living patients. The T stage was a strong prognostic factor, with a 5-year overall survival rate of 84% and 53% for T2 and T3 lesions, respectively, in patients <80 years old. CONCLUSION: This is the first report of long-term local control and survival for ultrasound-staged T2-T3 rectal adenocarcinoma treated by RT alone, showing that high-dose irradiation to a small volume can provide a high therapeutic ratio for such tumors.     

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

: 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.

: 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.

: 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.

: HDR fractionated interstitial brachytherapy can be an alternative to traditional LDR brachytherapy for early tongue cancer and eliminate the radiation exposure for medical staffs.     

Irradiation in carcinoma of the vulva: factors affecting outcome

Purpose: This report reviews the increasing role of radiation therapy in the management of patients with histologically confirmed vulvar carcinoma, based on a retrospective analysis of 68 patients with primary disease (2 in situ and 66 invasive) and 18 patients with recurrent tumor treated with irradiation alone or combined with surgery.Methods and Materials: Of the patients with primary tumors, 14 were treated with wide local excision plus irradiation, 19 received irradiation alone after biopsy, 24 were treated with radical vulvectomy followed by irradiation to the operative fields and inguinal–femoral/pelvic lymph nodes, and 11 received postoperative irradiation after partial or simple vulvectomy. The 18 patients with recurrent tumors were treated with irradiation alone. Indications and techniques of irradiation are discussed in detail.Results: In patients treated with biopsy/local excision and irradiation, local tumor control was 92% to 100% in Stages T1-3N0, 40% in similar stages with N1-3, and 27% in recurrent tumors. In patients treated with partial/radical vulvectomy and irradiation, primary tumor control was 90% in patients with T1-3 tumors and any nodal stage, 33% in patients with any T stage and N3 lymph nodes, and 66% with recurrent tumors. The actuarial 5-year disease-free survival rates were 87% for T1N0, 62% for T2-3N0, 30% for T1-3N1 disease, and 11% for patients with recurrent tumors; there were no long-term survivors with T4 or N2-3 tumors. Four of 18 patients (22%) treated for postvulvectomy recurrent disease remain disease-free after local tumor excision and irradiation. In patients with T1-2 tumors treated with biopsy/wide tumor excision and irradiation with doses under 50 Gy, local tumor control was 75% (3 of 4), in contrast to 100% (13 of 13) with 50.1 to 65 Gy. In patients with T3-4 tumors treated with local wide excision and irradiation, tumor control was 0% with doses below 50 Gy (3 patients) and 63% (7 of 11) with 50.1 to 65 Gy. In patients with T1-2 tumors treated with partial/radical vulvectomy and irradiation, local tumor control was 83% (14 of 17), regardless of dose level, and in T3-4 tumors, it was 62% (5 of 8) with 50 to 60 Gy and 80% (8 of 10) with doses higher than 60 Gy. The differences are not statistically significant. There was no significant dose response for tumor control in the inguinal–femoral lymph nodes; doses of 50 Gy were adequate for elective treatment of nonpalpable lymph nodes, and 60 to 70 Gy controlled tumor growth in 75% to 80% of patients with N2-3 nodes when administered postoperatively after partial or radical lymph node dissection. Significant treatment morbidity included one rectovaginal fistula, one case of proctitis, one rectal stricture, four bone/skin necroses, four vaginal necroses, and one groin abscess.Conclusions: Irradiation is playing a greater role in the management of patients with carcinoma of the vulva; combined with wide local tumor excision or used alone in T1-2 tumors, it is an alternative treatment to radical vulvectomy, with significantly less morbidity. Postradical vulvectomy irradiation in locally advanced tumors improves tumor control at the primary site and the regional lymphatics in comparison with reports of surgery alone.     

Carcinoma of the tonsillar fossa: prognostic factors and long-term therapy outcome

Purpose: To identify prognostic parameters and evaluate the therapeutic outcomes for patients with carcinoma of the tonsillar fossa treated with three treatment modalities.

Methods and Materials: The results of therapy are reported in 384 patients with histologically proven epidermoid carcinoma of the tonsillar fossa; 154 were treated with irradiation alone (55–70 Gy), 144 with preoperative radiation therapy (20–40 Gy), and 86 with postoperative irradiation (50–60 Gy). The operation in all but four patients in the last two groups consisted of an en bloc radical tonsillectomy with ipsilateral lymph node dissection.

Results: Treatment modality and total irradiation doses had no impact on survival. Actuarial 10-year disease-free survival rates were 65% for patients with T1 tumors, 60% for T2, 60% for T3, and 30% for T4 disease. Patients with no cervical lymphadenopathy or with a small metastatic lymph node (N1) had better disease-free survival (60% and 70%, respectively) at 5 years than those with large or fixed lymph nodes (30%). Primary tumor recurrence (local, marginal) rates in the T1, T2, and T3 groups were 20–25% in patients treated with irradiation and surgery and 31% for those treated with irradiation alone (difference not statistically significant). In patients with T4 disease treated with surgery and postoperative irradiation, the local failure rate was 32% compared with 86% with low-dose preoperative irradiation and 47% with irradiation alone (p = 0.03). The overall recurrence rates in the neck were 10% for N0 patients, 25% for N1 and N2, and 35–40% for patients with N3 cervical lymph nodes, without significant differences among the various treatment groups. The incidence of contralateral neck recurrences was 8% with the various treatment modalities. On multivariate analysis the only significant factors for local tumor control and disease-free survival were T and N stage (p = 0.04–0.001). Fatal complications were noted in 7 of 144 (5%) patients treated with preoperative irradiation and surgery, 2 of 86 (2%) of those receiving postoperative irradiation, and 2 of 154 (1.3%) patients treated with radiation therapy alone. Other moderate or severe nonfatal sequelae were noted in 30% of the patients treated with preoperative irradiation and surgery, in 53% treated with postoperative irradiation, and in 19% receiving radiation therapy alone.

Conclusion: Primary tumor and neck node stage are the only significant prognostic factors influencing locoregional tumor control and disease-free survival. Treatment modality had no significant impact on outcome. Radiation therapy remains the treatment of choice for patients with stage T1–T2 carcinoma of the tonsillar fossa. In patients with T3–T4 tumors and good general condition, combination surgery and postoperative irradiation offers better tumor control than single-modality and preoperative irradiation procedures, but with greater morbidity.     

Clinical results of proton beam therapy for cancer of the esophagus

PURPOSE: To present the results of proton beam therapy for patients with esophageal cancer. METHODS AND MATERIALS: This study reviewed 46 patients with esophageal cancer who were treated between 1985 and 1998 using proton beams with or without X-rays. All patients had locoregionally confined disease; all but one had squamous cell carcinoma. Of the 46 patients, 40 received combinations of X-rays (median, 48 Gy) and protons (median, 31.7 Gy) as a boost. The median total dose of combined X-ray and proton radiation for the 40 patients was 76.0 Gy (range, 69.1-87.4 Gy). The remaining 6 patients received only proton beam therapy (median, 82.0 Gy; range, 75-89.5 Gy). RESULTS: The 5-year actuarial survival rate for the 46 patients, patients with T1 (n = 23), and those with T2-T4 (n = 23) was 34%, 55%, and 13%, respectively. The 5-year disease-specific survival rate for the 46 patients, those with T1, and those with T2-T4 was 67%, 95%, and 33%, respectively. The 5-year local control rate for patients with T1 and T2-T4 lesions was 83% and 29%, respectively. The site of the first relapse was locoregional for 16 patients and distant organs for 2 patients. CONCLUSION: The results suggest that proton beam therapy is an effective treatment for patients with locally confined esophageal cancer. Additional studies are required to determine the optimal total dose, fractionation schedule, and best combinations of protons and conventional X-rays with or without chemotherapy.     

Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy.

EORTC protocol 22791 compared once daily fractionation (CF) of 70 Gy in 35-40 fractions in 7-8 weeks, to pure hyperfractionation (HF) of 80.5 Gy in 70 fractions in 7 weeks using 2 fractions of 1.15 Gy per day, in T2-T3 oropharyngeal carcinoma (excluding base of tongue), N0,N1 of less than 3 cm. From 1980 to 1987, 356 patients were entered. In the final analysis (June 1990), the local control was significantly higher (p = 0.02 log-rank) after HF compared with CF. At 5 years, 59% of patients are local disease-free in the HF arm compared to 40% in the CF arm. The superiority of HF was demonstrated in patients staged T3N0,T3N1 but not in T2. The Cox model confirmed that the treatment regimen was an independent significant prognostic factor for locoregional control (p = 0.007 log-rank). This improvement of locoregional control was responsible for a trend to an improved survival (p = 0.08 log-rank). There was no difference in late normal tissue damage between the two treatment modalities.     

Radiation therapy for T1,2 glottic carcinoma: impact of overall treatment time on local control

Purpose: Local control probabilities of T1,2 glottic laryngeal cancer were evaluated in relation to dose and fractionation of radiation therapy (RT). Materials and methods: Between 1975 and 1993, 96 T1N0M0 glottic cancers and 32 T2N0M0 glottic cancers were treated with definitive RT. Total RT dose was 60–66 Gy/2 Gy for most of the T1 and T2 tumors, although 10 T2 tumors were treated with hyperfractionation (72–74.4 Gy/1.2 Gy bid). Of the 128 patients, 90 T1 glottic tumors and 30 T2 glottic tumors were followed for >2 years after treatment. Multivariate analyses using the Cox proportional hazards model and a logistic regression analysis were performed to evaluate the significance of prognostic variables on local control. Results: The 5-year local control probability for T1 tumors was 85%, whereas that for T2 tumors was 71%. Multivariate analyses demonstrated that only overall treatment time (OTT) was a significant variable for local control. Total RT dose, normalized total doses at a fraction size of 2 Gy, and fraction size were not significant. Local control probability of T1 tumors with an OTT of 42–49 days was significantly higher than that of tumors with an OTT of >49 days (P < 0.02). Only a 1-week interruption of RT, due to holidays, significantly reduced the 5-year local control probability of T1 glottic tumors from 89 to 74% (P < 0.05). Conclusions: These results indicate that OTT is a significant prognostic factor for local control of T1 glottic tumors.     

Cancer of the anal canal: report on the experience of 61 patients

We report our experience on 61 anal canal epidermoid carcinoma bearing patients. The patients are divided into three therapeutic groups: a) 14 patients treated with combined surgery and preoperative radiotherapy (37.8 Gy in 18 fractions and 21 days); b) 28 patients treated with 60Co and electrontherapy (total tumor dose of 60 to 65 Gy); c) 19 patients treated with external cobaltherapy (30 Gy/10 fractions/12 or 15 days) followed 1 to 2 months later by interstitial brachytherapy with Iridium 192 (20 Gy). Local control was observed in 41 out of 61 patients (67.2%). Out of the six patients who underwent salvage abdomino-perineal resection, five were locally cured at 5 years. The overall 5-year survival is 78.6%; the corrected 5-year survival is 88.8%. Analysis of prognosis factors shows a direct relation between local control survival and the loco-regional extension. The 5-year survival was 90.9% in the first therapeutic group, 90.9% in the second group, and 94.7% in the third group. The 5-year survival rates according to the stage and to treatment were as follows: Stage T1 N0 100% in the 1st therapeutic group, 85.7% in the 2nd group, 100% in the 3rd group; for Stage T2 N0 80% in the 1st group, 90.9% in the 2nd group, 90% in the 3rd group; for Stage T3 N0 83.3% in the 1st group, 85.7% in the 2nd group, and 66.6% in the 3rd group. The rates of sphincter preservation were 85.7% in the 2nd group and 94.7% in the 3rd group. These results show the incidence of loco-regional extension on the prognosis and the usefulness of conservative treatments.     

Comparison between chemoradiation protocol intended for organ preservation and conventional surgery for clinical T1-T2 esophageal carcinoma.

PURPOSE: This retrospective study was designed to compare treatment results of the chemoradiation protocol with conventional surgery for thoracic T1-T2 esophageal squamous cell carcinoma. METHODS AND MATERIALS: Sixty-six patients with esophageal carcinoma, clinically diagnosed as T1 (tumor invading lamina propria or submucosa) or T2 (tumor invading muscularis propria) were treated for 12 consecutive years, from July 1986 to January 1998. The conventional surgery group included 30 patients who underwent esophagectomy with regional lymph node dissection. Twenty-one of them received postoperative radiotherapy. Thirty-six patients were assigned to the chemoradiation protocol, consisting of neoadjuvant chemoradiotherapy (44 Gy; CDDP: 60 mg/m2, day 1, bolus; 5-FU: 400 mg/m2, day 1-4, continuous), followed by either definitive radiotherapy with high-dose-rate intraluminal brachytherapy (total 70 Gy) for responders or surgery for nonresponders as in the conventional surgery group. Surgical candidates in both groups received intraoperative radiotherapy for abdominal lymphatics since 1991. RESULTS: In the protocol group, 4 patients underwent radical surgery after neoadjuvant chemoradiotherapy, and the remaining 32 underwent definitive chemoradiotherapy. Local control rates at 1 and 3 years were 85% and 70% in the T1/protocol group versus 91% and 80% in the T1/surgery group, and 83% and 83% in the T2/protocol group versus 94% and 80% in the T2/surgery group, respectively. There was no statistical significance. Overall 1- and 3-year survival rates were 100% and 83% in the T1/protocol group versus 82% and 72% in the T1/surgery group (p = 0.36), and 100% and 51% in the T2/protocol group, versus 95% and 68% in the T2/surgery group p = 0.61), respectively. There was no treatment-related mortality in either group. The rates of esophageal conservation were 92% in the T1/protocol group and 58% in the T2/protocol group. CONCLUSION: The chemoradiation protocol can result in comparable survival with conventional surgery for patients with T1-T2 esophageal carcinoma. A randomized trial between definitive chemoradiotherapy and surgery is required.     

Radiotherapy of carcinoma of the larynx--dose and function preservation

Relationship between irradiated dose and function preservation of the larynx in patients of laryngeal carcinoma (T1-T3) treated with radiotherapy were analysed and discussed. Local control rate for T1 and T2 lesion was highest in the dose range of 65-70 Gy. But in T3 lesion, especially of supraglottic cancer, the dose range to obtain highest local tumor control rate is above 76 Gy and higher than in case of T1 and T2 lesions. Laryngeal edema was seen in patients who were delivered the dose of 80 Gy. But total laryngectomy could be avoided by conservative therapy. Necessity of induction chemotherapy for advanced cases was also discussed.     

Impact of overall treatment time on local control of anal cancer treated with radiochemotherapy

Between 1987 and 2000, 111 patients with epidermoid anal cancer (T1-T4 Nx M0) were assigned to primary simultaneous radiochemotherapy (RCT) with a radiation dose of 45 Gy, performed either as a split course with 2-Gy single fractions (schedule A, 1987-1996, n = 65 patients) or continuously with fractions of 1.8 Gy (schedule B, 1996-2000; n = 38 patients). The chemotherapy consisted of continuous infusions of 5-fluorouracil (5-FU; 800/1,000 mg/m(2)/day, on 4/5 consecutive days, during weeks 1 and 5) together with one (schedule A) or two (schedule B) short infusions of mitomycin C (10 mg/m(2)) during the first course of 5-FU. Associations between clinical outcome and various prognostic factors were assessed in 103 patients who completed these schedules. For both patient groups combined, 5-year local control rate was 67% and 5-year survival rate 71%. Advanced tumor stage, size, and nodal status significantly decreased the 5-year local control rate as well as the overall treatment time (OTT) >41 days (58% for OTT >41 days vs. 79% for OTT < or =41 days; p = 0.04). However, we did not find a correlation with the prescribed radiotherapy schedule (A or B). In conclusion, in patients with anal carcinomas treated with RCT with a radiation dose of 45 Gy, the predominant determinant of local control is the resulting OTT and not the administration schedule (split course or continuous radiotherapy).     

16例原发腮腺鳞癌的治疗与预后

目的回顾分析16例腮腺鳞癌的临床特点和治疗结果,研究原发腮腺鳞癌预后影响因素及恰当的治疗方案。方法搜集1984-2005年收治并经病理证实的原发腮腺鳞癌16例,其中T1期2例,T2期5例,T3期5例,T4期4例。NO期10例,N＋期6例,单一手段治疗组6例（单纯手术5例,单纯放疗1例）,综合治疗组（手术加放疗）10例。结果全组患者在病程中出现颈部淋巴结转移的概率为75%（12/16）,全组3和5年局部控制率、总生存率、无瘤生存率分别为45%和30%、58%和58%、36%和27%。T1～T2和T3～T4期的5年生存分别为100%和29%,（X^2=4．50,P= 0．034）。NO和N＋期的3年总生存率分别为80%和20%（X^2=8．70,P=0．003）,无瘤生存率分别为54%和0（X^2=9．83,P=0．002）。结论原发腮腺鳞癌颈部淋巴结转移概率和局部复发率均高,应该采用手术加放射的综合治疗;N＋期患者术后应该给予同侧全颈及锁骨上区放疗;手术治疗时未行颈清扫者应行同侧全颈及锁骨上区预防照射。     

Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients

PURPOSE: To evaluate the impact of tumor response; tumor and nodal downstaging; and cTNM, yTNM (clinical stage after chemoradiation, based on preoperative imaging), and pTNM classifications on long-term outcome in patients with rectal cancer treated with preoperative 5-fluorouracil (5-FU)-based concurrent chemoradiation. METHODS AND MATERIALS: Between January 1990 and March 1998, 165 consecutive patients with locally advanced extraperitoneal cancer of the rectum were treated with preoperative chemoradiation. Four patients had a cT2 lesion (2.5%), 120 had a cT3 lesion (74.5%), and 41 had a cT4 lesion (23%). The nodal involvement at combined imaging was cN0 in 21%, cN1 in 41%, cN2 in 34%, and cN3 in 4%. Preoperative chemoradiation was delivered according to 1 of 3 schedules: (1) FUMIR-T3 (from 1990 to 1995) for patients with cT3N0-2 or cT2N1-2 rectal carcinoma (82 patients): 37.8 Gy (1.8 Gy/fraction) plus 5-FU, 1 g/m(2)/d on Days 1-4, continuous infusion, and mitomycin-C, 10 mg/m(2)/d on Day 1; (2) FUMIR-T4 (from 1990 to 1999) for patients with cT4N0-3 or cT3-4N3 rectal carcinoma (40 patients): 45 Gy (1.8 Gy/fraction) plus 5-FU, 1 g/m(2)/d on Days 1-4 and 29-32, continuous infusion, and mitomycin-C, 10 mg/m(2)/d on Days 1 and 29; and (3) PLAFUR-4 (from 1995 to 1998) for patients with cT3N0-2 or cT2N1-2 rectal carcinoma (42 patients): 50.4 Gy (1.8 Gy/fraction) plus 5-FU, 1 g/m(2)/d on Days 1-4 and 29-32, continuous infusion, and cisplatin, 60 mg/m(2)/d on Days 1 and 29. Four to five weeks after chemoradiation, patients were reevaluated for clinical response by imaging studies (CT scan, transrectal ultrasonography, barium enema, liver ultrasonography, chest X-rays) and restaged (yTNM). Surgery was performed 6-8 weeks after chemoradiation. Adjuvant chemotherapy (5-FU + l-folinic acid) was delivered to 26 patients in the FUMIR-T4 protocol group. Local control (LC), freedom from distant metastases (FDM), disease-free survival, and overall survival (OS) were evaluated according to the clinical response and cTNM, yTNM, and pTNM classification. The median follow-up was 67 months. RESULTS: The 5-year survival rate was 100% for cT2, 77% for cT3, and 62% for cT4 (p = 0.0497); after chemoradiation, it ranged between 81% and 91% for pT0-pT2 and dropped to 66% for pT3 and 47% for pT4 (p = 0.014). The 5-year local control rate was, at the first staging, 84% for cT3 and 72% for cT4; after chemoradiation, the pT stage correlated significantly with LC (p = 0.0012): 100% for pT0, 83% for pT1, 88% for pT2, 79% for pT3, and 46% for pT4. N stage was statistically significant in predicting FDM and OS at any staging step. A significant impact of tumor response, tumor downstaging, and nodal downstaging on LC, FDM, disease-free survival, and OS was also recorded. If the residual tumor, before surgery, had a tumor index <30 (i.e., width less than one-quarter of rectal circumference and length in its caudocranial axis < or =30 mm), the 5-year LC, FDM, disease-free survival, and OS rates were significantly higher at both the univariate and the multivariate analyses. The surgical procedure was tailored according to tumor downstaging, and thus the choice of sphincter-preserving surgery was based on the distance between the lower pole of the tumor and the anorectal ring "after" chemoradiation. In 36 patients with the lower pole of the lesion in the range of 0-30 mm from the anorectal ring, 16 patients (44%) underwent a sphincter-saving procedure. All clinical outcomes were similar compared with 20 patients with tumor located at the same rectum level who received an abdominoperineal resection. CONCLUSION: After preoperative chemoradiation, clinical response and tumor/nodal pathologic downstaging showed a close correlation with improved outcomes. The better 5-year survival and local control in pT0-2 patients regardless of their initial stage seems to confirm a heterogeneity in rectal cancer patients. The responder population showed a behavior similar to rectal cancer diagnosed at Stage cT1-2 and treated with conservative surgery alone. Additional studies aimed at improving local tumor response seem justified. Trials of sphincter-saving surgery after a major response are warranted.     

T1-T2N0 squamous cell carcinoma of the glottic larynx treated with radiation therapy.

PURPOSE: The end results after radiation therapy for T1-T2N0 glottic carcinoma vary considerably. We analyze patient-related and treatment-related parameters that may influence the likelihood of cure. PATIENTS AND METHODS: Five hundred nineteen patients were treated with radiation therapy and had follow-up for >or= 2 years. Three patients who were disease-free were lost to follow-up at 7 months, 21 months, and 10.5 years. No other patients were lost to follow-up. RESULTS: Local control rates at 5 years after radiation therapy were as follows: T1A, 94%; T1B, 93%; T2A, 80%; and T2B, 72%. Multivariate analysis of local control revealed that the following parameters significantly influenced this end point: overall treatment time (P < .0001), T stage (P = .0003), and histologic differentiation (P = .013). Patients with poorly differentiated cancers fared less well than those with better differentiated lesions. Rates of local control with laryngeal preservation at 5 years were as follows: T1A and T1B, 95%; T2A, 82%; and T2B, 76%. Cause-specific survival rates at 5 years were as follows: T1A and T1B, 98%; T2A, 95%; and T2B, 90%. One patient with a T1N0 cancer and three patients with T2N0 lesions experienced severe late radiation complications. CONCLUSION: Radiation therapy cures a high percentage of patients with T1-T2N0 glottic carcinomas and has a low rate of severe complications. The major treatment-related parameter that influences the likelihood of cure is overall treatment time.     

Radiation therapy of squamous cell carcinoma of the nasal vestibule

From 1978 until 1988, 63 consecutive patients with squamous cell carcinoma of the nasal vestibule were treated by radiation therapy. Mean follow-up time was 46 months. Thirty-five patients were classified as having T1N0 tumors, 24 as T2N0; four patients were staged as T1/2N+. Treatment of the primary consisted of external radiation (n = 17), interstitial radiation (n = 37), or external radiation combined with interstitial radiation (n = 9). With respect to the N0 patients, local relapse was found in 3% (1/35) of T1 tumors and in 21% (5/24) of T2 tumors. Three out of six failures were salvaged by surgery. Elective irradiation of both sides of the neck (40 Gy) was performed in 9 T1 and in 16 T2 patients. Two regional failures occurred in the electively irradiated necks, two in the non-irradiated necks. Regarding the T1/2N+ patients, three relapsed locally and/or regionally, and one remains NED. For all 63 patients, a 5-year corrected survival of 90%, a relapse-free survival of 80%, and an overall survival of 65% were observed. In summary, for optimal local control and cosmesis we feel that for T1,2 N0 tumor stages a dose of 60 Gy for T1 and 70 Gy for T2 tumors is adequate treatment. The primary tumor is irradiated preferentially in our view, by means of interstitial techniques; furthermore, our data do not support the use of elective neck RT. Although patients rarely present with lymph node metastasis (6%), the prognosis of T1,2 N+ patients remains grim and more aggressive (surgical) treatment might be needed for this category.