Relapse-free Rate Research Articles

Prognostic significance of pretreatment hemoglobin for local control and overall survival in T1-T2N0 larynx cancer treated with external beam radiotherapy

Purpose To elucidate a relationship between pretreatment hemoglobin and local control in patients with T1-T2N0 larynx cancer treated with radiotherapy. Methods and materials A total of 246 patients with T1-T2N0 cancer of the larynx were included in this analysis. Patients were treated using a median daily fraction of 200 cGy to a total median dose of 66 Gy within 47 days. Prognostic factors included pretreatment hemoglobin, age, gender, race, T stage, tumor subsite, beam energy, biologically equivalent dose, and therapy duration. Results Fifty patients developed local relapse, for an actuarial 5-year relapse-free rate of 77.3%. The actuarial 5-year survival rate was 69.8%. The pretreatment hemoglobin levels were assessed using the following hemoglobin quartiles: 10.1–13.3, 13.4–14.1, 14.2–14.9, and 15.0–18.3 g/dL. On Cox multivariate analysis, the pretreatment hemoglobin level predicted for local failure and poorer overall survival. The relative risk for 5-year local relapse by hemoglobin quartile was 2.70, 2.33, 1.91, and 1.00 ( p = 0.034). The relative risk for poorer 5-year overall survival by hemoglobin quartile was 2.23 1.30, 0.80, and 1.00 ( p <0.001). Conclusion Pretreatment hemoglobin levels predicted for local control and overall survival for larynx cancer in a multivariate model. This relationship has potential therapeutic implications regarding correcting anemia before the initiation of radiotherapy for optimal outcome.

Ultimate results of radiation therapy for T1-T2 mycosis fungoides (including reirradiation)

Purpose We report on our experience in the treatment of T1 and T2 mycosis fungoides (MF) with total skin electron beam therapy (TSEBT), with respect to relapse-free rate, overall survival rate, and management of recurrence. Methods and materials Between 1975 and 2001, 141 patients with MF were referred to the radiotherapy department for treatment by TSEBT. A total of 57 patients were staged as having T1 or T2 disease (24 T1 and 33 T2 patients). A total of 25 received topical therapy before irradiation. Treatment was delivered through a 6-MeV linear accelerator to a mean total dose of 30 Gy, 2 Gy/day, 4 days/week, for 4 weeks. Close follow-up was initiated without adjuvant therapy. Median age was 61 years (range, 19–84), and median follow-up was 114 months (range, 14–300). Results Three months after completion of TSEBT, the overall response rate was 94.7%. A complete response was achieved in 87.5% of T1 and 84.8% of T2 patients. Thirty-one patients (54.4%) experienced a skin failure (8 with T1 and 23 with T2 disease) within 1 year. Eighteen patients of 31 received a reirradiation as salvage therapy (6 localized treatment with segmental fields of electron beam irradiation and 12-second TSEB delivering 24 Gy in 12 fractions). Two were treated by topical steroids, and 11 received combination therapy with PUVA (2/10), topical (10/10) or systemic (4/10) chemotherapy, or interferon (7/10). After a second course of TSEBT (4 T1 and 10 T2 patients), the 5-year freedom from relapse rate was 70% vs. 39% in patients having received other modalities. For the whole group, 5-year DFS was 50%. The 5/10/15-year OS were 90%/65%/42%, respectively. In univariate analysis, T1 ( p = 0.03), CR after first TSEBT ( p = 0.04), and age younger than 60 ( p < 0.001) were significant prognostic factor for OS. In multivariate analysis, age younger than 60 years was statistically associated with improved OS ( p = 0.001); T stage and completion of CR remained under threshold of significance ( p = 0.059 and p = 0.063, respectively). During the mean 86-month period of follow-up from relapse, a second recurrence was observed in 29% of patients. Conclusions TSEBT is highly effective in early-stage MF without adjuvant therapy. Management of relapses with local radiotherapy or second TSEBT is feasible, time-saving, and cost-effective.

Appropriate radiation volume for stage IIA/B testicular seminoma

Purpose Prophylactic left supraclavicular fossa irradiation has been suggested to reduce relapse rates in patients treated for Stage IIA/B testicular seminoma. To address this issue, we reviewed patterns of failure and treatment outcome in patients treated with radiation therapy at our institution. Methods and materials Between 1981 and 1999, 79 men with Stage II seminoma (IIA, 49; IIB, 30) were treated with radiation therapy (RT) to the para-aortic and ipsilateral (± contralateral) pelvic lymph nodes (dose: 25–35 Gy). Results With a median follow-up of 8.5 years, the 5-year relapse-free rate was 91% (standard error: 3%), and 2 patients have died of seminoma, giving a 5-year cause-specific survival of 97%. A total of 7 patients have relapsed with 2 isolated to the left supraclavicular fossa. Five of 7 patients have been successfully salvaged. Conclusions Prophylactic left supraclavicular fossa irradiation might have prevented relapse in 2 of 79 patients in Stage IIA/B seminoma. However, 97% of patients would have received unnecessary left neck RT, so we continue to recommend, as standard treatment, infradiaphragmatic RT only.

Rotational 3D-conformal radiation therapy (conformation therapy) combined with hormone therapy for the treatment of stage B2/C prostate cancer in Japanese men

Background and purpose In our institution, rotational 3D-conformal radiation therapy (also called conformation therapy) has been applied since the late 1970s to conform the target volume of high-dose radiation to the cancerous tissue while minimizing radiation to the surrounding normal tissues. This technique has been used most commonly to treat prostate cancers in combination with hormonal therapy. The results of Stage B2/C prostate cancer treated with this method were analyzed. Patients and methods Between 1987 and 1997, 33 cases of prostate cancer were definitively treated with this method: 9 Stage B2 tumors and 24 Stage C tumors. Of these 33 tumors, 3 were well differentiated, 18 were moderately differentiated, and 12 were poorly differentiated. The average patient age was 75.6 years. The median pretreatment PSA value was 23.8 ng/ml. The total radiation dose ranged from 60 Gy to 70 Gy (average: 63.5 Gy) with conventional fractionation. Hormone therapy was administered permanently; the primary hormonal agent was diethylstilbestrol phosphate. Results The overall survival rate after 5 years was 58.2% and that after 10 years was 29.6%. The biochemical relapse–free rate after 5 years was 87.0% and that after 10 years was still 87.0%. There were 4 cases of biochemical failure, but no cases of death from prostate cancer. Stage, differentiation, and pretreatment PSA value were not prognostic factors. One of the 2 cases with delayed complications was a case of RTOG Grade 3 gastrointestinal complication. Conclusion Rotational 3D-conformal radiation therapy combined with hormone therapy might be promising for the treatment of prostate cancer.

Limitation of conventional two dimensional radiation therapy planning in nasopharyngeal carcinoma

Purpose: To assess the adequacy of coverage of gross tumor volume (GTV) with traditional two dimensional (2D) radiation therapy (RT) planning in patients with nasopharyngeal cancer (NPC). Materials and methods: The study comprised 94 of 179 patients treated with definitive RT between 1993 and 1997. The inclusion requirement was the availability of a digitally archived pretreatment magnetic resonance imaging. The digital images were used to record the precise location of the GTV in the sagittal plane. As a separate procedure, sagittal dose distributions for each treatment phase were created by digitizing the simulation field parameters into treatment planning software without knowledge of the GTV. The location of the GTV and dose distribution in the sagittal plane were superimposed on each other and GTV coverage by the 50, 90 and 95% isodose lines determined for each phase of treatment. Results: The 1997 tumour node metastasis (TNM) stage distribution was: 7 (8%) stage I, 16 (16%) stage II, 30 (32%) stage III and 41 (44%) stage IV. Median follow-up was 4.4 years. Median primary dose was 66 Gy. The actuarial 5-year overall survival, disease free survival and local relapse free rates were 88, 54 and 66%, respectively. The GTV was covered by the 50, 90 and 95% isodose lines for all phases of the multiphase plan in only 53, 20 and 9% of patients, respectively. The GTV was more likely to be undercovered in the latter phases of the plan particularly in those patients with advanced T category. Conclusion: 2D RT planning has significant limitations in achieving adequate GTV coverage in NPC. We strongly recommend 3D planning using either conformal techniques of dose delivery or intensity modulated radiation therapy for the treatment of these patients.

Surgical resection and radiotherapy for primary retroperitoneal soft tissue sarcoma

Methods and materials: Forty-five patients were consecutively treated for primary retroperitoneal soft tissue sarcoma with surgery in combination with radiation therapy in the same institution. The median follow-up time was 53 months (7–108). Results: Seventeen (38%) patients had clear microscopic margins (R0 resection), 26 patients (58%) had gross complete surgical excision (R1 resection) and two patients (4%) had a macroscopic residual disease (R2 resection). External radiotherapy doses ranged from 40.8 to 59.4 Gy (mean and median: 49 Gy). Seventeen patients underwent intraoperative radiation therapy (IORT). Moreover, 11 patients received chemotherapy. The overall 1-, 2-, and 5-year survival for all 45 patients were 93, 85 and 60%, respectively. The 1-, 2-, and 5-year locoregional relapse-free rate for the whole group was 91, 70 and 40%, respectively. In univariate analysis, quality of surgery was the only variable to show a significant effect for overall survival ( P=0.0386) and for local control ( P=0.0059). Tumor size and tumor grade had no statistically significant effect. For the patients receiving IORT+external beam radiation therapy, no difference was observed for survival or locoregional control. The most frequent acute side effects treatment complications were radiation-induced nausea or vomiting (42%) and moderate enteritis (30%). Significant late morbidity was observed for two patients. Conclusions: This study confirms the feasibility of external postoperative radiotherapy with an acceptable level of toxicity. However, the high rate of local relapses (especially in field of radiation) does not demonstrate the usefulness of radiotherapy at the level of dose used and further preferably randomized studies should be planned.

Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis.

Several management options are available to patients with stage I seminoma, including adjuvant radiotherapy, surveillance, and adjuvant chemotherapy. We performed a pooled analysis of patients from the four largest surveillance studies to better delineate prognostic factors associated with disease progression. Individual patient data were obtained from each center (Princess Margaret Hospital, Danish Testicular Cancer Study Group, Royal Marsden Hospital, and Royal London Hospital) for 638 patients. Tumor characteristics (size, histologic subtype, invasion of rete testis, and tumor invasion into small vessels [SVI]) as well as age at diagnosis were analyzed for prognostic importance for relapse. With a median follow-up of 7.0 years (range, 0.02 to 17.5 years), 121 relapses were observed for an actuarial 5-year relapse-free rate (RFR) of 82.3%. On univariate analysis, tumor size (RFR: <or= 4 cm, 87%; > 4 cm, 76%; P =.003), rete testis invasion (RFR: 86% [absent] v 77% [present], P =.003), and the presence of SVI (RFR: 86% [absent] v 77% [present], P =.038) were predictive of relapse. On multivariate analysis, tumor size (<or= 4 cm v > 4 cm, hazard ratio 2.0; 95% confidence interval [CI], 1.3 to 3.2) and invasion of the rete testis (hazard ratio 1.7; 95% CI, 1.1 to 2.6) remained as important predictors for relapse. We have identified size of primary tumor and rete testis invasion as important prognostic factors for relapse in patients with stage I seminoma managed with surveillance. This information will allow patients and clinicians to choose management based on a more accurate assessment of an individual patient's risk of relapse. In addition, it will allow clinicians to tailor follow-up protocols based on risk of occult disease.

(IN)-efficacy of salvage radiotherapy for rising PSA or clinically isolated local recurrence after radical prostatectomy

Purpose: To determine the efficacy of external beam radiotherapy (RT) as salvage treatment for prostate-specific antigen (PSA) failure or local recurrence after radical prostatectomy.Methods and Materials: Between 1991 and 1997, 98 patients underwent salvage RT to the prostatic bed at the Toronto Sunnybrook Regional Cancer Centre for PSA failure or local recurrence after radical prostatectomy. Thirty-six patients were treated for persistently detectable postoperative PSA levels (Group A), 26 for a delayed PSA rise (Group B), and 36 for palpable and/or biopsy-proven local recurrence (Group C). None had clinically apparent distant metastasis at the time of salvage RT. Freedom from PSA failure was defined as the maintenance of PSA ≤0.2 ng/mL. Cox regression analyses were performed to identify factors predictive of relapse.Results: The median follow-up from radical prostatectomy and RT was 5.11 and 4.21 years for Group A, 5.31 and 3.32 years for Group B, and 7.85 and 3.95 years for Group C, respectively. The initial PSA response rate was encouraging at a range of 86—94%. The complete PSA response rate (PSA ≤0.2 ng/mL) was lower, however and ranged from 53% to 62%. The actuarial relapse-free rate, including freedom from PSA failure, at 4 years was 26%, 39%, and 14% for Groups A, B, and C, respectively. At the time of the last follow-up, 49, 20, and 1 patient had PSA failure alone, distant metastasis, and local progression, respectively. The actuarial survival rate at 4 years was 89%, 95%, and 94% for Groups A, B, and C, respectively. On Cox regression analysis, the significant predictors for relapse were PSA level before salvage RT and Gleason score for Group A, none for Group B, and margin status for Group C.Conclusion: The efficacy of salvage RT for PSA failure or local recurrence after RT was limited, reflected by very low relapse-free rates. Salvage RT appeared more efficacious for patients with a delayed PSA rise than for those with either persistently detectable postoperative PSA levels or clinically palpable local recurrence. Other strategies such as a combination of salvage RT and hormonal therapy need to be explored.

Results of radiotherapy for primary subglottic squamous cell carcinoma

Purpose : To retrospectively evaluate the outcome after radical radiotherapy (RT) and surgical salvage and assess the risk of late toxicity for patients with primary subglottic squamous cell carcinoma treated at our center. Methods and Materials : Between 1971 and 1996, 43 patients with primary squamous cell carcinoma of the subglottis (35 men, 8 women) were treated with radical RT. All received megavoltage irradiation, most commonly to a dose of 50–52 Gy in 20 fractions during 4 weeks (39 patients). The median follow-up was 4.2 years. Results : Local control was achieved with RT alone in 24 (56%) of the 43 patients: 7 of 11 with T1, 8 of 12 with T2, 4 of 8 with T3, and 5 of 12 with T4. The 5-year actuarial local relapse-free rate was 52%. Subsequent local control was achieved in 11 of the 13 patients with failed RT and attempted surgical salvage, for an ultimate local control rate of 81.4% (35 of 43). The 5-year overall and cause-specific actuarial survival rate was 50.3% and 66.9%, respectively. No patients developed Grade 3 or 4 late radiation morbidity. Conclusion : These data support the use of primary RT in the treatment of patients with primary squamous cell carcinoma of the subglottis as an appropriate treatment approach providing an option for laryngeal conservation.

Radiotherapy management for squamous cell carcinoma of the nasal skin: the Princess Margaret Hospital experience

Purpose: To evaluate the outcome of radiotherapy (RT) for squamous cell carcinoma (SCC) of the nasal skin.Methods and Materials: The charts of 100 patients referred and treated with RT during 1982 to 1993 for SCC of nasal skin were reviewed. Most patients (81%) were treated with orthovoltage X-rays. In general, lesions ≤2 cm were treated to 35 Gy in 5 fractions. For tumors 2–5 cm, 45 Gy in 10 fractions was commonly used. Lesions >5 cm or those associated with bone or cartilage invasion were typically treated to 50 Gy in 20 fractions. Six patients were lost to follow-up, leaving 94 patients assessable for local or regional failure analysis. Using the UICC staging system, the T stage at first presentation was as follows: T1, 60 patients; T2, 11 patients; T3, 0 patients, T4, 7 patients; TX, 16 patients. Only 1 patient had regional lymph node disease at presentation. Thirty-one patients were treated with surgery, followed by RT. Sixty-three patients were treated with primary RT.Results: The local relapse-free rate was 90% and 85% at 2 and 5 years, respectively. The actuarial 2 and 5-year overall survival rate was 75% and 51%, respectively. The cause-specific survival was 96% at both 2 and 5 years. No Radiation Therapy Oncology Group Grade 4 toxicities occurred. Univariate analysis could not identify any patient, tumor, or treatment factors that were statistically significant prognosticators.Conclusion: RT for SCC of nasal skin achieves excellent outcome, is well tolerated, and should continue to be recommended in the management of this disease.

Positive resection margin and/or pathologic T3 adenocarcinoma of prostate with undetectable postoperative prostate-specific antigen after radical prostatectomy: to irradiate or not?

Purpose : To evaluate the efficacy of postoperative adjuvant radiotherapy (RT) for positive resection margin and/or pathologic T3 (pT3) adenocarcinoma of the prostate with undetectable postoperative prostate-specific antigen (PSA) levels. Methods and materials : We retrospectively analyzed 125 patients with a positive resection margin and/or pT3 adenocarcinoma of the prostate who had undetectable postoperative serum PSA levels after radical prostatectomy. Seventy-three patients received postoperative adjuvant RT and 52 did not. Follow-up ranged from 1.5 to 12.0 years (median 4.2 for the irradiated group and 4.9 for the nonirradiated group). PSA outcome was available for all patients. Freedom from failure was defined as the maintenance of a serum PSA level of ≤0.2 ng/mL, as well as the absence of clinical local recurrence and distant metastasis. Results : No difference was found in the 5-year actuarial overall survival between the irradiated and nonirradiated group (94% vs. 95%). However, patients receiving adjuvant RT had a statistically superior 5-year actuarial relapse-free rate, including freedom from PSA failure, compared with those treated with surgery alone (88% vs. 65%, p = 0.0013). In the irradiated group, 8 patients had relapse with PSA failure alone. None had local or distant recurrence. In the nonirradiated group, 15, 1, and 2 had PSA failure, local recurrence, and distant metastasis, respectively. On Cox regression analysis, pre-radical prostatectomy PSA level and adjuvant RT were statistically significant predictive factors for relapse, and Gleason score, extracapsular invasion, and resection margin status were not. There was a suggestion that seminal vesicle invasion was associated with an increased risk of relapse. The morbidity of postoperative adjuvant RT was acceptable, with only 2 patients developing Radiation Therapy Oncology Group Grade 3 genitourinary complications. Adjuvant RT had a minimal adverse effect on urinary continence and did not cause serious gastrointestinal toxicity. Conclusion : Postoperative adjuvant RT was associated with a lower risk of relapse, including freedom from PSA failure, compared with observation alone for pT3 and/or margin-positive disease with undetectable postoperative PSA levels. This was accomplished with a minimal risk of serious RT morbidity.

New Electroablation Technique Following the First-Line Stapling Method for Thoracoscopic Treatment of Primary Spontaneous Pneumothorax

A new tip for the electroablation of pneumocysts was examined clinically as a second-line method for stapled resection of pneumocysts during video-assisted thoracoscopic surgery (VATS). A trial to assess feasibility. National referral hospitals. One hundred seven patients were studied, of whom 99 patients were eligible for the study (85 men and 14 women; age range, 15 to 69 years; median age, 23 years), who had undergone VATS for primary spontaneous pneumothorax between July 1996 and June 1998. Apical pneumocysts were resected employing staplers, and residual pneumocysts, if present, were electroablated employing a new tip for the electrosurgery unit (ball shape, 8 mm in diameter, and made of stainless steel). Thirty-three patients (33%) underwent electroablation only for small (< 2 cm in diameter) pneumocysts (group S), and 11 patients (11%) underwent electroablation for large (>/= 2 cm in diameter) pneumocysts (group L). The remaining 55 patients (56%) did not undergo electroablation because there were no residual pneumocysts (group N). There were no complications during surgery. The duration of the operation was significantly shorter (about 20 min on average) for group N, but there was no significant difference in the amount of blood loss, the number of applied staples, the duration of drainage, and the duration of hospital stay. Group S achieved a 100% relapse-free rate (33 of 33 patients), group L achieved a 64% relapse-free rate (7 of 11 patients), and group N achieved an 89% relapse-free rate (49 of 55 patients) [group S vs group N, p = 0.08; group L vs group N, p = 0.001; and group S vs group L, p = 0.002]. Electroablation with the M-tip is feasible as a second-line method for the treatment of small pneumocysts following the stapling technique during VATS.

CLINICAL COURSE and RELAPSE RATE IN INTESTINAL BEHCET'S DISEASE

Behçet's disease is a multisystemic recurrent inflammatory disease. Gastrointestinal tract involvement in Behçet's disease has been identified throughout the alimentary tract and causes diverse symptoms. Various treatment have been utilized to induce or maintain remission. However, little is known about clinical course and prognosis in Behçet's disease with intestinal involvement. The aims of this study were to evaluate the clinical course and relapse rate in intestinal Behçet's disease and to investigate factors that may affect relapse.Methods Clinical course and characteristics, including demographic parameters, gastrointestinal symptoms as well as systemic manifestations, laboratory data, endoscopic findings, and treatment strategies for the induction of remission, of 97 patients (49 male, 48 female) with intestinal Behçet's disease were retrospectively reviewed. Cumulative relapse free rate and factors related with relapse were analysed by Kaplan–Meier method and log–rank test, respectively.Results The median duration of the relapse free period was 7 months (ranges from 1 to 171 months). One, two, and five year relapse free rates were 41.2, 29.7 and 10.2%, respectively. Sex, clinical subtype of Behçet's disease, symptom and laboratory data at onset, colonoscopic findings, such as distribution of lesions as well as number, size, depth, and shape of ulcer, and initial treatment (medical vs. surgical) did not affect relapse rate. However, large ulcers (&gt; 20 mm) and young age at onset (&lt; 37 years old) were factors significantly related with higher relapse rate (P &lt; 0.05, log–rank test).Conclusion High relapse rate in intestinal Behçet's disease was identified. Age at onset and size of the ulcer are factors related with long‐term prognosis of intestinal Behçet's disease.

Local excision and postoperative radiotherapy for distal rectal cancer

Purpose: To assess the outcome following local excision and postoperative radiotherapy (RT) for distal rectal carcinoma. Materials and Methods: Seventy-three patients received postoperative radiotherapy following local surgery for primary rectal carcinoma at Princess Margaret Hospital from 1983 to 1998. Selection factors for postoperative RT were patient preference, poor operative risks, and “elective” where conservative therapy was regarded as optimal therapy. Median distance of the primary lesion from the anal verge was 4 cm (range, 1–8 cm). There were 24 T1, 36 T2, and 8 T3 lesions. The T category could not be determined in 5. Of 55 tumor specimens in which margins could be adequately assessed, they were positive in 18. RT was delivered using multiple fields by 6- to 25-MV photons. Median tumor dose was 50 Gy (range, 38–60 Gy), and 62 patients received 50 Gy in 2.5-Gy daily fractions. The tumor volume included the primary with 3–5 cm margins. No patients received adjuvant chemotherapy. Median follow-up was 48 months (range, 10–165 months). Results: Overall 5-year survival and disease-free survival were 67% and 55%, respectively. Tumor recurrence was observed in 23 patients. There were 14 isolated local relapses; 6 patients developed local and distant disease; and 3 relapsed distantly only. For patients with T1, T2, and T3 lesions, 5-year local relapse-free rates were 61%, 75%, and 78%, respectively, and 5-year survival rates were 76%, 58%, and 33%, respectively. The 5-year local relapse-free rate was lower in the presence of lymphovascular invasion (LVI) compared to no LVI, 52% vs. 89%, p = 0.03, or where tumor fragmentation occurred during local excision compared to no fragmentation, 51% vs. 76%, p = 0.02. Eleven of 14 patients with local relapse only underwent abdominoperineal resection, 8 achieved local control, and 4 remained cancer free. The ultimate local control, including salvage surgery, was 86% at 5 and 10 years. The 5-year colostomy-free rate was 82%. There were 2 patients who experienced RTOG Grade 3 late complications, and 1 with Grade 4 complication (bowel obstruction requiring surgery). Conclusion: The local relapse rate for patients with T1 disease was high compared to other series of local excision and postoperative RT. Patients with LVI or tumor fragmentation during excision have high local relapse rates and may not be good candidates for conservative surgery and postoperative RT.

Breast-conserving therapy for ductal carcinoma in situ.

This retrospective analysis evaluates the treatment results and prognostic factors of 114 patients with ductal carcinoma in situ (DCIS) undergoing breast conserving therapy (BCT) at Keio University Hospital Department of Radiology, between 1988 and 1997. A total of 132 patients with DCIS of the breast came to our hospital between 1988 and 1997, and 114 cases were suitable candidates for BCT. All of the patients were female and ranged in age from 26 to 81 years (median 46). Ninety-one patients were premenopausal, and 23 were postmenopausal. Median clinical tumor size was 2.0 cm (0-8.0 cm). Postoperatively 48 cases received 50 Gy/25 fractions of external irradiation to the whole breast via tangential ports. The follow-up period after treatment ranged from 11 to 162 months (median 46.7). The local relapse-free rate and overall survival rate of the 114 patients were 89.5% and 100%, respectively. Local failure and regional nodal failure occurred in 12 and 1 patient, respectively. Radiotherapy was a significant risk factor for local failure (p=0.05). No postmenopausal patients developed local failure, but the difference did not reach statistical significance (p=0.103). The 12 recurrent cases underwent additional surgery and all remain alive without recurrence, to date, i.e., at least 16 months. Breast-conserving surgery plus irradiation is appropriate treatment for DCIS patients.

Squamous Cell Carcinoma of the Oesophagus Treated with Radiation and 5-Fluorouracil, with and without Mitomycin C

A retrospective analysis was performed of patients with squamous cell carcinoma of the oesophagus without evidence of distant metastases, who were treated with radical intent. Between 1981 and 1984, and 1989 and 1991, 98 patients were treated with radiation, 5-fluorouracil (5-FU) and mitomycin C; and between 1984 and 1989, 133 patients were treated with radiation and 5-FU without mitomycin C. Actuarial survival and local control were assessed, and prognostic factors were identified for both endpoints. The standard dose of radiation prescribed was 52 Gy to the 95% isodose in 20 fractions over 4 weeks. 5-FU was given by continuous infusion as 1g/m2 (maximum 1.5g)/day, for 4 days. Patients who received mitomycin C were given 10mg/m2 (maximum 18mg) on day 1. Survival and local relapse-free rates were estimated using the method of Kaplan and Meier, and the Cox proportional hazards model was used to evaluate possible prognostic factors, including the effect of mitomycin C administration.The median survival was 15.4 months (95% confidence interval 12.7–17.2) with 31% 2-year survival (standard error (SE) 3%), and 13% 5-year survival (SE 2%). In the multivariate analysis, lower radiation dose and younger age were the only statistically significant prognostic factors for reduced overall survival and reduced relapse-free rate respectively. There was no difference in survival (χ2 = 0.07, 1 degree of freedom (df), P = 0.79) or local relapse-free rate (χ2 = 0.39, 1 df, P = 0.53) between patients treated with or without mitomycin C. The treatment was well tolerated. Further studies are required to determine the most effective combination of radiation and chemotherapy or other radiation sensitizers for squamous cell carcinoma of the oesophagus.

Hemodynamics in the left gastric vein after endoscopic ligation of esophageal varices combined with sclerotherapy.

We examined the changes in portal hemodynamics after endoscopic variceal ligation (EVL) combined with endoscopic injection sclerotherapy (EIS) in relation to post-treatment relapse. The present study included 93 patients who underwent EVL-EIS combination therapy. Portal hemodynamics were examined by Doppler ultrasonography and percutaneous transhepatic portography (PTP). Therapy with EVL-EIS resulted in the complete disappearance of varices in 89 of 93 patients. Cumulative relapse-free rates (Kaplan-Meier method) were 75.8 and 50.2%, respectively, 1 and 3-5 years after treatment. At the end of treatment, the flow in the left gastric vein was examined by Doppler ultrasonography. In 50 of 63 patients, the flow remained hepatofugal. In 23 of these patients, PTP was performed at the end of treatment; selective left gastric venography did not reveal any palisade zone vessels or varices. However, fine blood vessels were seen around the lower esophagus in nine patients, only the paraesophageal vein was found in 10 patients and these two findings were present in four patients, indicating that collateral blood flow remained in the lower esophagus in 13 of 23 patients. These findings suggest that frequent relapse of varices results from insufficient blockage of blood flow from the left gastric vein to the lower esophagus. However, in patients with a patent paraesophageal vein, long-term effects obtained by EVL-EIS combination therapy were satisfactory. The pattern of the development of collateral left gastric veins represents important hemodynamic changes that predict the long-term prognosis of patients after treatment.

Adjuvant and salvage radiation therapy after radical prostatectomy for adenocarcinoma of the prostate

Purpose: To evaluate the outcome of adjuvant and salvage radiotherapy (RT) after radical prostatectomy (RP) for clinically localized prostate cancer using conventional clinical end-points, and the biochemical relapse-free rate (bRFR). Methods: Between 1987 and 1994, 113 node negative, hormonally naı̈ve men received RT 1 month to 12 years after RP. Adjuvant RT was given for positive resection margins and/or pT3 disease. Salvage RT was given for a persistently elevated prostatic specific antigen (PSA), a rising PSA, or palpable recurrence post RP. Clinical and biochemical endpoints determined outcome. Log-rank testing and the Cox proportional hazards model identified factors predictive for biochemical relapse free rate. Results: Median follow-up after RT was 3.7 years (range 0.2–9 years). Five-year clinical local control was 95% for patients with no palpable evidence of disease and 59% for those with palpable recurrence ( P<0.0001). 5-year bRFR was 81% for adjuvant RT, 19% for salvage of biochemical recurrence, 0% for patients with palpable disease ( P<0.0001). Improved bRFR for adjuvant and salvage RT was predicted by a Gleason score <7 vs. 7 vs. >7 (hazard ratio 1.53; 95% CI 0.99–2.35) and an undetectable pre-RT PSA vs. PSA <2.0 ng/ml vs. PSA >2.0 ng/ml (hazard ratio 3.81; 95% CI 2.47–5.87). Seminal vesicle involvement was not a statistically significant independent predictor of bRFR. Conclusions: The most favourable bRFR was observed for adjuvant therapy. Salvage was most successful with a pre-RT PSA <2.0 ng/ml, or Gleason score <7. Few patients with a pre-RT PSA >2.0 ng/ml were salvaged, and none with palpable recurrence. These patients require investigation of alternative salvage strategies.

The impact of irregularly rising prostate-specific antigen and “impending failure” on the apparent outcome of localized prostate cancer following radiotherapy

Purpose: To examine the impact of irregularly rising prostate-specific antigen (PSA) and “impending” biochemical failure on the apparent rate of biochemical relapse following radiotherapy for localized prostate cancer. Methods and Materials: We analyzed the outcome of 572 patients with T1/T2 prostate cancer treated with radiotherapy alone at the Princess Margaret Hospital (median follow-up, 4.21 years). Biochemical outcomes were analyzed using 2 different definitions of failure: ( 1) the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, and ( 2) a modified definition that included 2 consecutive rises in PSA, with a minimum rise of 1.5 ng/mL above the nadir, or a nadir value of greater than 4 ng/mL. Patients were defined as having “impending failure” when the last 2 PSA measurements taken demonstrated 2 consecutive rises. Results: Two-hundred and thirty patients (40%) met the ASTRO definition of failure; 258 patients (48%) failed by the modified definition ( p = 0.001). Five-year biochemical relapse-free rate (bNED) rate was 55% using the ASTRO definition, and 49% using the modified definition. This difference in 5-year bNED was greatest for patients with high-risk disease (ASTRO definition 30% vs. modified definition 15%). Twenty-four of the 38 additional cases identified as biochemical failures by the modified definition had irregularly rising PSA levels; 14 were “impending failures.” These additional 38 patients had a median PSA elevation 5.4 ng/mL above the nadir, and a high risk of subsequent clinical failure (4-year clinical failure-free rate of 63%). The ASTRO definition had a sensitivity of 87% and specificity of 74% for predicting clinical relapse. The modified definition had a sensitivity of 95% and a specificity of 70%. Conclusion: A definition of biochemical failure that includes an absolute allowable rise in PSA above the nadir can identify patients with rising PSA who are at substantial risk of clinical relapse, but who are not defined as biochemical failures by the ASTRO definition. This is particularly true for patients with high-risk disease. The use of a uniform definition of biochemical failure is crucial to ensure that differences in apparent outcome are not due to differences in the definition of relapse. Currently, the ASTRO definition should remain the standard. Large cohort studies with long follow-up can be utilized to optimize the definition of biochemical failure following radiotherapy for prostate cancer.

True recurrence vs. new primary ipsilateral breast tumor relapse: An analysis of clinical and pathologic differences and their implications in natural history, prognoses, and therapeutic management

Purpose: The purpose of this study was to classify all ipsilateral breast tumor relapses (IBTR) in patients treated with conservative surgery and radiation therapy (CS+RT) as either new primary tumors (NP) or true local recurrences (TR) and to assess the prognostic and therapeutic implications of this classification. Methods and Materials: Of the 1152 patients who have been treated at Yale–New Haven Hospital before 1990, 136 patients have experienced IBTR as their primary site of failure. These relapses were classified as either NP or TR. Specifically, patients were classified as NP if the recurrence was distinctly different from the primary tumor with respect to the histologic subtype, the recurrence location was in a different location, or if the flow cytometry changed from aneuploid to diploid. This information was determined by a detailed review of each patient’s hospital and/or radiotherapy record, mammograms, and pathologic reports. Results: As of 2/99, with a mean follow-up of 14.2 years, the overall ipsilateral breast relapse-free rate for all 1152 patients was 86% at 10 years. Using the classification scheme outlined above, 60 patient relapses were classified as TR, 70 were classified as NP and 6 were unable to be classified. NP patients had a longer mean time to breast relapse than TR patients (7.3 years vs. 3.7 years, p < 0.0001) and were significantly younger than TR patients (48.9 years vs. 54.5 years, p < 0.01). Patients developed both TR and NP at similar rates until approximately 8 years, when TR rates stabilized but NP rates continued to rise. By 15 years following original diagnosis, the TR rate was 6.8% compared to 13.1% for NP. Of the patients who had been previously tested for BRCA1/2 mutations, 17% (8/52) had deleterious mutations. It is noteworthy that all patients with deleterious mutations had new primary IBTR, while patients without deleterious mutations had both TR and NP ( p = 0.06). Ploidy was evenly distributed between TR and NP but NP had a significantly lower S phase fraction (NP 13.1 vs. TR 22.0, p < 0.05). The overall survival following breast relapse was 64% at 10 years and 49% at 15 years. With a mean follow-up of 10.4 years following breast relapse, patients with NP had better 10-year overall survival (TR 55% vs. NP 75%, p < 0.0001), distant disease-free survival (TR 41% vs. NP 85%, p < 0.0001), and cause-specific survival (TR 55% vs. NP 90%, p < 0.0001). Conclusion: It appears that a significant portion of patients who experience ipsilateral breast tumor relapse following conservative surgery and radiation therapy have new primary tumors as opposed to true local recurrences. True recurrence and new primary tumor ipsilateral breast tumor relapses have different natural histories, different prognoses, and, in turn, different implications for therapeutic management.