The value of postexcision preradiation mammography in patients with early-stage breast cancer

The purpose of this study was to evaluate the benefit of postexcision preradiation mammography for patients with early-stage breast cancer. The records of 101 patients (103 breasts) with either ductal carcinoma in situ (DCIS) or early invasive breast cancer diagnosed based on microcalcifications on a mammogram between January 1999 and December 2001 at our institution were reviewed. Sixty-one patients had a postexcision preradiation mammogram, and 42 patients did not have a mammogram until the completion of radiation. Of the 61 patients who had a preradiation mammogram, 1 patient (2%) was found to have residual microcalcifications after the completion of chemotherapy. A core biopsy revealed DCIS, and a wide excision revealed no additional abnormalities. Of the 42 patients who underwent a postradiation mammogram, 1 patient had calcifications in the same quadrant as her original biopsy. A wide excision revealed only sclerosing adenosis. For women who receive chemotherapy before the initiation of radiation, a preradiation mammogram ought to be considered because there will frequently be a 6-month interval from the patient's lumpectomy to the initiation of radiation. However, for women scheduled to start radiation within an interval of 4 months or less, our data do not support the routine use of postexcision preradiation mammography. Although we recognize that our data may not be representative of the community at large, our observations do not support the routine use of postexcision preradiation mammography in women with small breast cancers.     

Radiation therapy (RT) after prostatectomy: The case for salvage therapy as opposed to adjuvant therapy

Patients with pathologic stage T3 or T4 prostate cancer who have undetectable PSA levels following radical retropubic prostatectomy (RRP) have a substantial risk of recurrence. Radiotherapy (RT) can be administered immediately following the RRP (immediate adjuvant RT) or may be postponed until the PSA level has risen to a level that is indicative of residual or recurrent prostate cancer (salvage RT). Immediate adjuvant RT can significantly reduce the risk of relapse, but does not appear to increase the rate of survival. Approximately two-thirds of patients with rising PSA levels after RRP can be salvaged with RT alone. This result was achieved in patients treated with an adequate dose of radiation before the PSA rose to > 1.1 ng/ml. While no one can be certain which approach (adjuvant or salvage RT) is better, future studies should examine this issue. Whether immediate postoperative adjuvant RT is of value to patients is the subject of two randomized prospective studies. The benefit of adjuvant RT is a matter of controversy. Salvage RT treats only those patients with proven residual prostate cancer. The salvage RT approach has several advantages. This approach spares approximately 40% of patients who have had an RRP for T3 or T4 prostate cancer and eliminates the risks and costs associated with adjuvant RT. Additionally, it appears that the results of immediate adjuvant RT are similar to those achieved with early salvage RT.     

Process and preliminary outcome of a patterns-of-care study of esophageal cancer in Japan: patients treated with surgery and radiotherapy

PURPOSE: To evaluate the quality of radiotherapy (RT) in Japan, we have been carrying out a national survey through patterns-of-care studies (PCSs) since 1996. We present the preliminary results of surgery combined with RT with or without chemotherapy for thoracic esophageal cancer. METHODS AND MATERIALS: A Japanese PCS data format for esophageal cancer was established based on one used in the United States and including information used in the surgical registration system in Japan, so that the results in both countries could be compared. An independent panel of radiation oncologists surveyed randomly selected institutions and patients between September 1998 and March 2001. There were 767 esophageal cancer patients, of whom 220 had undergone preoperative or postoperative RT. RESULTS: The median age of the 220 patients was 62.3 years (range 31-89); of them, 88.1% were men. Pathologically, 218 patients (99.5%) had squamous cell carcinoma, predominantly located in the middle and lower thoracic esophagus, 41.7% of the patients had Stage III disease; they accounted for 52.6% of patients in nonacademic institutions and for 37.7% of those in academic institutions (p = 0.016). Sixty-nine patients received preoperative RT; of them, 60.9% received chemotherapy; 145 patients received postoperative RT with or without chemotherapy. The spinal cord of 23 (11.7%) of 196 patients was irradiated with >/=50 Gy. In academic institutions, extended radical "three-field" lymphatic dissection was performed for 72 (48.7%) of 148 patients; however, this sophisticated surgical procedure was done in only 13 (25.5%) of 51 patients in nonacademic settings (p = 0.004). In all large academic institutions (those treating >/=300 patients annually), >/=6 MV of photon energy was used; 30.5% of nonacademic institutes had linear accelerators of <6 MV photon (p = 0.001). No deviations occurred in the radiation dose (median 46 Gy), fractionations, or fields between the two types of institutions. Univariate analyses showed that the statistically significant prognostic factors affecting overall survival were stage (p = 0.001), extended radical "three-field" lymphatic dissection (p = 0.001), no residual tumor (p = 0.001), supraclavicular RT (p = 0.001), mediastinal RT (p = 0.025), Karnofsky performance status (p = 0.006) photon energy (p = 0.011), and stratification of the institutions (p = 0.001). Multivariate analysis showed that the type of institution (p = 0.045, risk ratio = 0.604), stage (p 0.029, risk ratio = 0.572), no residual tumor (p = 0.006, risk ratio = 0.487), photon energy (p = 0.043, risk ratio = 0.579), and use of chemotherapy (p = 0.012, risk ratio = 1.907) significantly affected overall survival. CONCLUSION: This PCS showed that in Japan important issues are present regarding RT for esophageal cancer that should be solved immediately, namely, treatment strategy, photon energy, and dose applied to the spinal cord. The PCS provided important information on how much improvement in structure and process would be required nationwide for RT of esophageal cancer.     

Outcomes of patients receiving radiation for carcinoma of the rectum. Results of the 1988-1989 patterns of care study

BACKGROUND: Clinical trials of surgical adjuvant treatment for patients with rectal carcinoma (RC) indicate that postoperative radiation therapy with concurrent chemotherapy (CRT) is superior to postoperative radiation alone (RT) or surgery alone. Whether preoperative treatment is superior to postoperative treatment is controversial. This Patterns of Care Study (PCS) surveyed patients with RC treated with radiation during the years 1988-1989 to determine the national practice standards and outcomes and to compare these results with those of clinical trials. METHODS: A national survey of 73 institutions was conducted using 2-stage cluster sampling, and specific information on 406 patients with RC who received radiation at 69 facilities was collected. Follow-up information on 215 patients was subsequently collected by mail survey. There were no significant differences between the known prognostic indicators or treatment-related variables for patients for whom follow-up was available compared with the variables for patients for whom follow-up was not available. Follow-up ranged from 0 to 8.44 years with a median of 4 years. One hundred fifty-four patients (71%) received postoperative treatment, either RT (37%) or CRT (34%); and 40 (18%) received preoperative treatment, either RT (15%) or CRT (3%). Ninety-six patients (45%) received chemotherapy, and for 86% of those patients chemotherapy was administered concurrently with radiation. RESULTS: Survival was stage-dependent (85% Stage I, 69% Stage II, and 54% Stage III at 5 years, P = 0.04). Survival was also substage-dependent, and patients with C(1) cancer had significantly higher 5-year survival than those with C(2)/C(3) cancer (89% vs. 48%, P = 0.008). Local failure was similar for Stage II and Stage III patients (10% vs. 11% at 5 years, respectively). In multivariate analyses, only stage and use of chemotherapy were significant to survival (Stage III vs. Stage I and II, relative risk [RR] = 2.52, and chemotherapy vs. no chemotherapy, RR = 0.46). A significantly higher 5-year survival rate was seen with postoperative CRT than with postoperative RT (69% vs. 50%, P = 0. 011). Preoperative radiation resulted in a significantly higher 5-year survival rate than postoperative radiation (85% vs. 50%, P = 0.0006), but not compared with postoperative CRT. Survival and local failure did not differ according to radiation therapy interruption or the interval between surgery and radiation. CONCLUSIONS: Stage is an important prognostic indicator for survival, and among patients with Stage III malignancies survival in the substage C(1) is significantly higher than in the substages C(2) and C(3). As has been demonstrated in randomized trials, adjuvant postoperative CRT is superior to postoperative RT for patients with RC in this national study. These nationwide results of adjuvant treatment are comparable to those reported in randomized trials. The use of CRT was the only treatment-related factor that resulted in a significant reduction in the risk of death.     

Surgery and postoperative radiation therapy in stage II endometrial carcinoma.

The traditional approach to patients with stage II endometrial carcinoma is preoperative radiation therapy (RT) followed by surgery. Currently, many patients are treated with primary surgery and postoperative RT. We retrospectively reviewed the outcome of 44 stage II (32 IIA, 12 IIB) patients who underwent surgery and postoperative RT. Nine (20%) had microscopic cervical involvement noted before surgery, and 35 (80%) had occult involvement noted postoperatively. Postoperative RT consisted of whole pelvic RT (WPRT) (50%), vaginal brachytherapy (VB) (18%), or both (32%). At a median follow-up of 40 months, the 5-year actuarial disease-free survival was 72.4%. Two patients (4%) had recurrence in the pelvis (one vagina, one lateral pelvis). Eighteen stage IIA patients treated with WPRT alone and eight stage IIA patients, without deep myometrial invasion (MI), were treated with VB alone, and remained controlled in the pelvis. Extrapelvic recurrences occurred in 12 patients (25%), primarily in those with deep MI and/or grade 2-3 disease. Our results suggest that patients with stage II endometrial carcinoma with microscopic or occult cervical involvement treated with surgery and postoperative RT have a favorable outcome. A high rate of pelvic control is achieved with RT tailored to the pathologic findings.     

Characteristics of 49 patients who survived for 5 years following radical radiation therapy for non-small cell lung cancer: the potential for cure

PURPOSE: To investigate the long-term curative potential of radical radiation therapy (RT) for non-small cell lung cancer (NSCLC) by studying characteristics of patients from a large prospective database who survived >5 years after RT, and by analyzing survival beyond 5 years. METHODS AND MATERIALS: Five-year survivors were identified from a database containing information on 488 patients given radical RT following presentation to the Peter MacCallum Cancer Institute with NSCLC between 1984 and 1990. Additional data were obtained from case notes of survivors. RT was computed tomography (CT)-planned, conventionally-fractionated, and given without chemotherapy. RESULTS: Actuarial survival for 49 5-year survivors was 65% at 10 years. Five 5-year survivors had documented disease progression within the first 5 years and subsequently died. Of 44 patients free-from-progression (FFP) at 5 years, an estimated 81% remained FFP in the second 5 years. Age and histology were not significant prognostic factors, and only 22 patients (4.5%) had weight loss >10%. For 277 patients who had not undergone thoracotomy, median RT dose was 60 Gy and survival at 5 and 10 years was 7% and 3%, respectively. For 207 patients who received radical RT post-thoracotomy, median dose was 60 Gy and survival at 5 and 10 years was 24% and 18%, respectively. Five-year survivors of post-thoracotomy RT had been treated for gross residual disease (n = 10), positive-margin (n = 6), or probable microscopic residual disease (n = 17). Failure to regain ECOG performance status = 0 post-thoracotomy was associated with reduced survival (p<0.0012). FFP in the second 5 years was superior for patients who had postoperative radiotherapy (90%) compared to patients without thoracotomy (62%, p = 0.008). CONCLUSION: Most patients FFP >5 years after radical RT for NSCLC remained FFP in the following 5 years and were apparently cured. RT alone can cure small but significant numbers of patients. Long-term results of combined chemotherapy/RT protocols, which are associated with increased median survival, are awaited for comparison.     

Preliminary analysis of a randomized clinical trial of adjuvant postoperative RT vs. postoperative RT plus 5-FU and levamisole in patients with TNM stage II-III resectable rectal cancer

OBJECTIVES: Two-hundred eighteen patients with TNM stage II-III resectable rectal cancer, enrolled into a randomized clinical trial, were assessed for efficacy and toxicity of adjuvant postoperative radiation therapy (RT) vs. those of combined RT and chemotherapy (CT), with 5-fluorouracil (5-FU) plus levamisole. End points were overall survival, disease-free survival, the rate of loco-regional recurrence, and treatment-related toxicity. METHODS: Patients in arm I underwent RT (50 Gy) in daily fractions of 2 Gy, 5 days/week for 5 weeks. Patients in arm II began with 5-FU (450 mg/m(2)/day intravenous bolus, days 1-5) plus levamisole (150 mg/day orally, days 1-3); postoperative RT was delivered during week 2 at the same dosage and schedule as in arm I. The other five cycles of CT (5-FU every 28 days and levamisole every 15 days for the length of 5-FU administration) continued after the end of RT if clinical and hemato-biochemical parameters were normal. RESULTS: RT was completed or modified in 170 (90%) of 189 evaluable patients undergoing RT (both treatment groups). Only 44 (59%) of 75 evaluable patients of arm II completed or had an adjustment of the CT schedule; the remaining 31 patients (41%) had to stop or never started the CT regimen. Patients undergoing combined RT and CT had more severe toxicity (enteritis, P = 0.03). There was one CT-related death (gastrointestinal bleeding) in this subset. No significant difference was observed in outcome of patients in the two study groups, nor for pattern of recurrence (heterogeneity chi(2) = 4.82; d.f. = 2; P = 0.08). CONCLUSIONS: These preliminary findings suggest a similar efficacy, coupled with less morbidity, of postoperative RT alone compared with a combined regimen of postoperative RT and CT in patients undergoing radical surgery for stage II-III rectal cancer.     

Breast conservation therapy: local tumor control in patients with pathologically clear margins who receive 5000 cGy breast irradiation without local boost

Summary A retrospective study was performed to determine the value of pathological evaluation of inked primary tumor specimen margins in the local control of patients with stage I and II breast cancer. In 150 patients with 153 invasive breast cancers, treatment involved surgical resection of the primary tumor, pathological determination of tumor-free inked specimen margins, and 5000 cGy whole breast radiation therapy (RT) without tumor bed RT local boost. This approach yielded an actuarial five-year local control rate of 95%. The local control rate was 96% for T-1 cases and 93% for T-2 cases. The local control rate was 96% for patients with clear margins achieved at initial resection and 94% for patients with clear margins achieved at re-excision. Among patients with clear margins at re-excision, the local control rate was 97% for those with no residual cancer and 88% for those with residual cancer. Patients with surgical margins clear by 3 mm or less had a local control rate of 92% at five years. Local control rates appear to be comparable to other breast conservation approaches which routinely employ local RT boosts. In omitting the local RT boost in patients with clear margins, the overall RT course will be briefer and the cosmetic changes associated with high-dose, large volume local RT boosts can be avoided.     

Conservative management of extensive low-lying rectal carcinomas with transanal local excision and combined preoperative and postoperative radiation therapy. A report of a phase I-II trial.

Between 1986 and 1990, 16 patients were enrolled in a prospective Phase I/II study of transanal local excision and combined preoperative and postoperative radiation therapy (RT). All patients had biopsy-proven adenocarcinoma extending to within 6 cm of the anal verge and involvement of at least one third of the rectal circumference with tumor. Five of 16 patients (32%) had T3 tumors, and only two patients had T1 tumors. Patients received a single 500 cGy fraction of RT to the pelvis within 24 hours before surgery and underwent transanal excision followed by postoperative RT (median dose, 5040 cGy). With a median follow-up of 33 months, overall 3-year actuarial survival was 94%. Two patients had isolated local recurrences (both successfully salvaged), and four had distant metastases but maintained local control. The 3-year actuarial rates of continuous freedom from any relapse, continuous local control, and no evidence of disease at last follow-up were 53%, 80%, and 71%, respectively. Only three of 16 patients required colostomy, resulting in a 3-year actuarial colostomy-free rate of 77%. There was a trend toward a higher rate of relapse (P = 0.066) in patients with T3 tumors than those with T1 and T2 tumors. Sphincter-preserving therapy for low-lying rectal carcinomas using local excision and combined preoperative and postoperative RT is feasible, although improved local and adjuvant therapy is needed for patients with T3 lesions.     

Pilot study of postoperative reirradiation, chemotherapy, and amifostine after surgical salvage for recurrent head-and-neck cancer

PURPOSE: Salvage surgery alone after radiotherapy (RT) failure for locally advanced head-and-neck cancer is frequently unsuccessful because of subsequent recurrence. We designed a prospective protocol to determine the feasibility, toxicity, and preliminary efficacy of a regimen of postoperative reirradiation, chemotherapy and the radioprotector amifostine after salvage head-and-neck surgery. METHODS AND MATERIALS: Eligible patients had biopsy-proven locally advanced, but resectable, recurrence without distant metastases >6 months after previous RT. After adequate healing from surgery, patients underwent RT to 54-66 Gy within 5-5.5 weeks to the resection bed (lifetime RT dose, 100-130 Gy). The fractionation was 1.5 Gy b.i.d. within 2 weeks, followed by a 1-week break, followed by 1.5 Gy b.i.d. to a total of 54-66 Gy. Chemotherapy consisted of cisplatin 25 mg/m(2)/d three times and 5-fluorouracil 500 mg/m(2)/d continuous infusion for 4 days, for two cycles (Weeks 1 and 5). Amifostine (500 mg i.v.) was administered daily, 30 min before either the morning or the afternoon RT. RESULTS: Between 1998 and 2001, 16 patients were enrolled and studied. Two patients had gross residual disease after surgery; all other patients underwent complete surgical resection but had high-risk features (rT3-T4 and/or N+ disease). Three patients (19%) had serious acute toxicity events (nonneutropenic infections) that were reversible. The median follow-up was 35 months. The actuarial locoregional control rate was 81% at 3 years. Three patients developed isolated distant metastases and one developed a fatal second primary cancer (hepatoma). The 2- and 3-year actuarial event-free survival rate was 81% and 50%, respectively. The 2- and 3-year actuarial overall survival rate was 81% and 63%, respectively. Both patients who had gross residual disease after surgery had early recurrence; if these patients were excluded from analysis, the 3-year actuarial survival and event-free survival rate was 67% and 59%, respectively. Of the 16 patients, 6 (38%) developed Grade 3+ late toxicity, including one fatal stroke and two life-threatening major vessel necrosis and/or bleeding events. CONCLUSION: This regimen of postoperative reirradiation/chemotherapy plus amifostine is feasible and was well tolerated acutely, with encouraging oncologic efficacy. However, the incidence and severity of late effects was significant and suggests that modifications are necessary for future studies in this patient population.     

Limited epithelial carcinoma of the ovary treated with curative intent by the intraperitoneal installation of radiocolloids.

Between January 1960 and September 1972, 104 patients with limited epithelial carcinoma of the ovary received intraperitoneal radiocolloid. Fifty-six of these patients also received external beam radiation therapy to the pelvis (pelvic RT). Five-year actuarial no-evidence-of-disease survival rates were 95% for stage Iai, 82% for Iaii, 73% for Ib, 67% for Ic, 67% for IIa, 67% for IIb without gross residual tumor (GRT), 25% for IIb with GRT, and 50% for III with minimal or no GRT. The addition of pelvic RT following radiocolloid could not be shown to affect survival of patients with Stage I and IIa tumors. Small bowel complications were related to the use of pelvic RT, however, occurring in 2.2% of patients treated with radiocolloid alone and 24% of patients treated with colloid and pelvic RT (p less than 0.005). In patients who underwent abdominal surgery following treatment of ovarian cancer, no excessive complication rate was observed. We conclude that for patients with stages Iaii through IIa, postoperative radiocolloid appears to provide the greatest chance of survival with the least chance of complication. For patients with Stage IIb and III lesions in whom there is minimal or no GRT, radiocolloid followed by pelvic RT produced survival rates comparable or superior to any other form of postoperative therapy.     

Resected pancreatic cancer treated with adjuvant radiotherapy with or without 5-fluorouracil: treatment results and patterns of failure.

There are relatively little data regarding patterns of recurrence after curative resection and postoperative radiotherapy with or without 5-fluorouracil (5-FU) for patients with adenocarcinonima of the pancreas. Between 1978 and 1997, 41 patients underwent postoperative radiotherapy (RT) at Loyola-Hines Department of Radiotherapy. Of the 38 evaluable patients, 30 had RT + 5-FU and 8 had RT alone. Twenty-nine patients (76.3%) had a Whipple's resection, seven (18.4%) had distal pancreatectomy, and two (5.2%) had total pancreatectomy. Thirty-three (86.8%) of the 38 patients received > or =4,500 cGy to the tumor bed. Median survival for all patients was 21 months. The median survivals for patients who received RT + 5-FU and RT alone were 26 months and 5.5 months (p = 0.004). The most common site of failure was the liver, as seen in 79.2% of all recurrences. The peritoneum, other distant sites (lungs, bone, distant lymph nodes), and locoregional tumor bed were components of failure in 33.3%, 29.2%, and 25.0%, respectively. Locoregional failure alone was found in only one patient. Our median survival with postoperative RT + 5-FU is consistent with results reported by the Gastrointestinal Tumor Study Group and Mayo Clinic. Although patients who had RT + 5-FU had a better median survival than those who received RT alone, our RT-alone group had an inferior survival outcome compared to other published reports and may represent patient selection bias. Efforts in controlling this disease should be directed to prevention of intraabdominal relapse.     

Results of re-excisional biopsy of the primary tumor in preparation for definitive irradiation of patients with early stage breast cancer

From December 1977 through November 1984, 251 patients underwent a re-excisional biopsy procedure in preparation for definitive radiation therapy because of uncertainty in the extent of the initial biopsy procedure. Analysis of the cases was limited to patients with AJC Clinical Stages I or II breast cancer and whose initial biopsy procedure demonstrated invasive carcinoma. Sixty-three percent (158/251) of the 251 re-excisions were positive for residual tumor, and 37% (93/251) did not show any residual tumor. Of the positive re-excisions, 85% (134/158) revealed an invasive component of tumor; 15% (24/158) revealed only non-invasive disease. For patients whose initial biopsy was described as incisional only, 97% (64/66) had residual tumor; 51% (94/185) of patients with an initial excisional biopsy had residual tumor. Because of the extremely high rate of positive re-excision in patients with an initial incisional biopsy, these cases were excluded from the remainder of the analysis. When the pathologic margin of the initial biopsy specimen was described as positive, 60% (15/25) had residual tumor on re-excision and 49% (79/160) when the pathology margin was unknown. Of the clinical T1 lesions, 45% (57/126) had positive re-excision, and of the clinical T2 lesions, 63% (37/59) were positive. When a post-biopsy mammogram (i.e. following initial biopsy procedure but before re-excision) showed residual microcalcifications, 86% (12/14) had residual tumor found in the re-excision specimen. Based on these findings, indications for re-excisional biopsy of the primary tumor are: initial incisional biopsy, positive or unknown pathologic margin on an initial excisional biopsy specimen, or residual microcalcifications on post-biopsy mammogram. When inked margins were negative on pathological examination of an initial excisional biopsy specimen, re-excision of the primary tumor bed was not recommended. These results suggest that a re-excisional biopsy procedure may be an important component of the overall treatment approach to assure removal of all tumor, and should continue to be used when indicated prior to definitive irradiation of the breast for early stage breast cancer.     

Operable Stages IB and II cervical carcinomas: a retrospective study comparing preoperative uterovaginal brachytherapy and postoperative radiotherapy

PURPOSE: To evaluate our data concerning prognostic factors and treatment toxicity in a series of operable cervical carcinomas. METHODS AND MATERIALS: Between May 1972 and January 1994, 414 patients with cervical carcinoma, staged according to the 1995 FIGO staging system (286 Stage IB1, 38 Stage IB2, 56 Stage IIA, and 34 Stage IIB with 1/3 proximal parametrial involvement), underwent radical hysterectomy with (n = 380) or without (n = 34) bilateral pelvic lymph node dissection (N+: n = 68). Group I included 168 patients who received postoperative radiation therapy (RT): 64 patients had low-dose-rate vaginal brachytherapy with a median total dose (MTD) of 50 Gy; 93 patients had external beam pelvic RT (EBPRT) with an MTD of 45 Gy over 5 weeks, followed by low-dose-rate vaginal brachytherapy (MTD: 20 Gy); and 11 patients had EBPRT alone (MTD: 50 Gy over 6 weeks). Group II included 246 patients treated with preoperative low-dose-rate uterovaginal brachytherapy (MTD: 65 Gy); 32 of these 246 patients also received postoperative EBPRT (MTD: 45 Gy over 5 weeks) delivered to the parametria and pelvic nodes. Mean follow-up from the beginning of treatment was 106 months. RESULTS: First events included isolated locoregional recurrences (35 patients), isolated distant metastases (27 patients), and locoregional recurrences with synchronous metastases (13 patients). The 10-year disease-free survival (DFS) rate was 88% for Stage IB1, 44% for Stage IB2, 65% for Stage IIA, and 48% for Stage IIB. Multivariate analysis showed that independent factors influencing the probability of DFS were as follows: cervical site (exocervical or endocervical vs. both endo- and exocervical, relative risk [RR]: 1.77, p = 0.047), vascular space invasion (no vs. yes, RR: 1.95, p = 0.041), age (>51 years vs. 1 cm: 83% vs. 41%, respectively, p = 0.001). The overall postoperative complication rate was 10% in Group I and 9% in Group II (p = 0.7). The rate of postoperative ureteral complications requiring surgical intervention was lower in Group I than in Group II (0.6% vs. 2.3%, respectively, p = 0.03). The overall 10-year rate for Grade 3 and 4 late radiation complications was 10.4%. Postoperative EBPRT significantly increased the 10-year rate for Grade 3 and 4 late radiation complications (yes vs. no: 22% vs. 7%, respectively, p = 0.0002). CONCLUSION: The prognosis for patients with cervical carcinoma was not influenced by the sequence of adjuvant RT (preoperative uterovaginal brachytherapy vs. postoperative RT) for Stages IB, IIA, and IIB with 1/3 proximal parametrial involvement. However, postoperative EBPRT increased the risk of late radiation complications.     

Preoperative chemotherapy followed by surgery with possible postoperative radiotherapy in squamous cell carcinoma of the esophagus: evaluation of the chemotherapy component

Twenty-four patients with squamous cell cancer of the esophagus were entered into a treatment protocol consisting of preoperative chemotherapy (CT), surgical resection (SR), and possible postoperative CT or radiation therapy (RT) beginning August 1981. CT consisted of two cycles of 5-fluorouracil, 1,000 mg/m2, by continuous intravenous infusion for 4 days and cisplatin, 100 mg/m2, on day 4 with mannitol-induced diuresis at 4-week intervals. Postoperatively, RT was administered when resection margins were minimal or if paraesophageal nodes were abnormal; the RT consisted of 5,000 to 5,400 cGy to the tumor area plus a 800- to 1,200-cGy boost to known abnormal tumor margins. Nineteen of 24 patients were resectable (79%). There was one SR death (5%). One of 22 had a normal barium swallow post-CT, no visible tumor at SR, and no pathologic evidence of any residual disease. There was complete radiologic and gross clinical disappearance of tumor post-CT or post-SR in ten of 22 patients (45%). Four of 22 (18%) had greater than or equal to 50% regression, and five of 22 (23%) had no response. Toxicity of CT was mild. Eight of 19 patients (42%) received RT, and six of 19 (32%) received CT postoperatively. Sixteen of 24 (67%) are alive with a median duration of observation of 9.5 months. Eight of 24 (33%) are dead, five of whom had not responded to preoperative CT. Ten of 14 responders are alive and disease free. The mean survival time for nonresponders was 6.70 months and for responders, 20.40 months, with the longest survivor disease free at 45 months.     

Early evaluation of the response to radiotherapy of patients with squamous cell carcinoma of the head and neck using 18FDG-PET

The aim was to evaluate the efficacy of positron emission tomography (PET) with 2-[F-18]fluoro-2-deoxy-d-glucose (FDG) in early discrimination of response to definitive radiotherapy (RT) in patients with squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients who underwent FDG-PET scans before and after radiotherapy for nondisseminated SCCHN at the Asan Medical Center between August 2001 and September 2002 were prospectively evaluated. Initial FDG-PET scans were performed within 1 month before RT, and follow-up FDG-PET scans were performed 1 month after completion of RT. FDG-PET images were analyzed by standard uptake value (SUV). All patients were followed for more than 6 months. Pretreatment SUV ranged from 3.4 to 14.0 (median, 6.0), while posttreatment SUV ranged from ground level to 7.7 (median, 2.0). In evaluating residual tumors in these SCCHN patients, the overall sensitivity of FDG-PET was 100%, while its overall specificity was 87%. FDG-PET is effective in evaluating the response to radiation in patients with SCCHN. Timing the follow-up FDG-PET scan 1 month after completion of RT was not too rapid for evaluating the response to radiation.     

Thoracic radiation therapy before autologous bone marrow transplantation in relapsed or refractory Hodgkin's disease. PMH Lymphoma Group, and the Toronto Autologous BMT Group

The aim of this study was to assess the relationship between radiation therapy (RT) and treatment-related mortality in patients receiving high-dose chemotherapy (HDCT) and autologous bone marrow transplantation (ABMT) for recurrent/refractory Hodgkin's disease (HD). Between December 1986 and December 1992, 59 patients previously treated at the Princess Margaret Hospital underwent HDCT (etoposide 60 mg/kg, melphalan 160 mg/m2) and ABMT, performed for refractory (13 patients) or relapsed (46 patients) HD. RT was incorporated in the salvage treatment with the intent to achieve complete control of disease prior to ABMT. RT was given before ABMT in 33 patients, and after ABMT in 4 patients. Treatment-related (TR) mortality was defined as any death occurring within 100 days of ABMT. Autopsies were performed for all patients with TR deaths. With a median follow-up of 4.6 years (range 1.2-7.4 years), the actuarial overall survival was 41% +/- 14% at 5 years. We observed 37 deaths, and 10 of these were TR deaths. Among the 24 patients who received thoracic RT before ABMT, there were 8 TR deaths, 3 of these solely attributable to radiation pneumonitis. The remaining 5 TR deaths all had respiratory failure with complicating sepsis as a major medical problem. The interval from RT to ABMT was shorter for 8 patients dying of TR death (mean 37 days; range 0-103 days), than for the 16 survivors (mean 105 days; range 0-263 days) (P = 0.026). Among 9 patients with ABMT within 50 days of thoracic RT, 6 had TR death. In contrast, among the 35 patients without thoracic RT (26 no RT, 9 non-thoracic RT), there were only 2 TR deaths. The 4 patients treated with mantle RT post-ABMT had no serious pulmonary complications. The use of thoracic RT before HDCT and ABMT was associated with a high post-transplant mortality rate. It was most evident in patients who received thoracic RT within 50 days prior to ABMT, or when the target volume included large volume of lung. We recommend that the use of post-transplant RT be investigated to decrease TR mortality.     

Results of salvage radiotherapy after inadequate surgery in invasive cervical carcinoma patients: a retrospective analysis

PURPOSE: To evaluate the results of salvage radiotherapy (RT) after inadequate surgery in patients with invasive carcinoma of the cervix. METHODS AND MATERIALS: Between 1996 and 2001, 105 invasive cervical carcinoma patients were treated at our center with external beam RT with or without intracavitary RT after having undergone total/subtotal hysterectomy at outside institutions. RESULTS: The median follow-up was 34 months. The gap between surgery and RT was 23-198 days (median, 80). Clinically visible residual disease was present in 81 patients (77.1%). Total hysterectomy had been done in 82 patients (78%) and subtotal hysterectomy in 23 patients (22%). The 5-year overall survival, disease-free survival, and pelvic control rates of all patients were 55.2%, 53.3%, and 72.4%, respectively. On univariate analysis, older age, total hysterectomy, hemoglobin level >10 g% before RT, nonsquamous histologic type, use of intracavitary RT, a shorter gap between surgery and RT, and the absence of, or a small volume of, residual disease favorably affected the outcome. The 5-year actuarial rate of late toxicity (Radiation Therapy Oncology Group Criteria) was 19% in the rectum, 4.8% in the bladder, 24.8% in the skin, and 14.3% in the small intestine. CONCLUSIONS: Inadequate and inappropriate surgery in invasive cervical cancer with resulting gross residual disease is common in India. Factors such as the use of intracavitary RT, the correction of anemia, and a shorter gap between surgery and RT will enable postoperative RT to achieve acceptable results with minimal morbidity.     

Multimodality therapy for CNS mixed malignant germ cell tumors (MMGCT): results of a phase II multi-institutional study

In order to improve outcomes for CNS mixed malignant germ cell tumors (MMGCT) we sought to increase complete responses (CR) to initial therapy, through intensifying neoadjuvant chemotherapy (CHT1) with added ifosfamide, encouraging second-look surgery, and administering dose-intensive, stem cell-supported chemotherapy (CHT2) to patients with residual tumor, all prior to radiation therapy (RT). Diagnosis was confirmed by biopsy or elevated germ cell tumor markers. After tumor staging was completed, patients received four cycles of chemotherapy (cisplatin, etoposide and ifosfamide, “CHT1”). In patients with <CR, second-look surgery was encouraged. Patients with residual tumor received two cycles of high dose, sub-ablative chemotherapy with carboplatin and cyclophosphamide (“CHT2”) with peripheral stem cell support. All patients then received RT: for localized tumors with CR before RT, 36 gray (Gy) whole ventricular radiation therapy (WVRT) plus 50.4 Gy boost to primary; for disseminated tumors or < CR before RT, craniospinal irradiation (CSI) plus boosts to primary site(s) and bulky metastases. 26 patients (19 M0, 7 M+) were enrolled. The diagnosis was established by histology (20) or elevated markers (6). Objective responses to CHT1 were complete in 12/22 patients with evaluable disease and partial in 10; 8 additional tumors were rendered CR prior to RT (5 surgical CRs: 3 initial, 2 second-look; 3 CRs to CHT2). Thus, 20/26 patients (77 %) were free of disease (CR) prior to RT. Six-year relapse-free survival was 63 ± 10 %; overall survival was 68 ± 9 %. Of 16 M0 patients who received only WVRT, four relapsed in the spine, outside the radiation field. The relatively high frequency (25 %) of relapse outside the initial RT volume highlights the limitations of initial staging criteria and the curative potential of conventional and high dose chemotherapy. CSI remains the standard of care for CNS MMGCT, even for patients with localized disease.     

The evaluation and treatment of patients receiving radiation therapy for carcinoma of the esophagus: results of the 1992-1994 Patterns of Care Study.

BACKGROUND: For the first time, a Patterns of Care Study (PCS) was conducted in 1992-1994 to determine the national practice standards in evaluating and treating patients with esophageal carcinoma and to determine the degree to which clinical trials have been incorporated into national practice. METHODS: A national survey of 61 institutions using 2-stage cluster sampling was conducted, and specific information was collected on 400 patients with squamous cell carcinoma or adenocarcinoma of the thoracic esophagus who received radiation therapy (RT) as part of definitive or adjuvant management of their disease. Patients were staged according to a modified 1983 American Joint Committee on Cancer staging system. Chi-square tests for significant differences between academic and nonacademic institutions for a particular variable were performed. RESULTS: The median age of patients was 66.7 years (range, 26-89 years); 76.5% were male and 23.5% were female. Karnofsky performance status was > or = 80 for 88.3% of patients. Squamous cell carcinoma was diagnosed in 61.5% and adenocarcinoma in 36.8%. Fifteen percent were Clinical Stage (CS) I, 39.5% CS II, and 29.5% CS III. Evaluative procedures included endoscopy (>93%), computed tomography (CT) of the chest (86%), CT of the abdomen (75%), esophagography (68.5%), and endoscopic ultrasound (3.5%). Endoscopic ultrasound and CT of the chest were performed significantly more frequently at academic than nonacademic facilities (6.1% vs. 1.0% and 91.9% vs. 81.3%, respectively). Three-quarters of all patients received chemotherapy and RT and 62.5% received concurrent chemotherapy and RT as part of their treatment. Treatments included chemotherapy plus RT (54.0%), RT alone (20.3%), preoperative chemotherapy + RT (13.3%), postoperative chemotherapy + RT (7.7%), postoperative RT (3.5%), and preoperative RT (1.2%). The chemotherapeutic agents most frequently used were 5-fluorouracil (84%), cisplatin (64%), and mitomycin (9%); academic instututions used cisplatin significantly more often and mitomycin significantly less often than nonacademic institutions. Brachytherapy was used in 8.5% of cases. The median total dose of external beam radiation was 50.4 gray and the median dose per fraction was 1.8 gray. CONCLUSIONS: This study establishes the national benchmarks for the evaluation and treatment of patients with esophageal carcinoma at radiation facilities in the U.S. It also indicates that the majority of patients given RT as a component of treatment for esophageal carcinoma receive chemoradiation rather than RT alone, as supported by clinical trials. Although some differences in the evaluation of esophageal carcinoma were noted between academic and nonacademic facilities, there was no difference in the frequency of use of chemoradiation versus RT by facility type.