Results of a pooled analysis of IOERT containing multimodality treatment for locally recurrent rectal cancer: Results of 565 patients of two major treatment centres.

OBJECTIVE: Aim of this study is analysing the pooled results of Intra-Operative Electron beam Radiotherapy (IOERT) containing multimodality treatment of locally recurrent rectal cancer (LRRC) of two major treatment centres. METHODS AND MATERIALS: Five hundred sixty five patients with LRRC who underwent multimodality-treatment up to 2010 were studied. The preferred treatment was preoperative chemo-radiotherapy, surgery and IOERT. In uni- and multivariate analyses risk factors for local re-recurrence, distant metastasis free survival, relapse free survival, cancer-specific survival and overall survival were studied. RESULTS: Two hundred fifty one patients (44%) underwent a radical (R0) resection. In patients who had no preoperative treatment the R0 resection rate was 26%, and this was 43% and 50% for patients who respectively received preoperative re-(chemo)-irradiation or full-course radiotherapy (p < 0.0001). After uni- and multivariate analysis it was found that all oncologic parameters were influenced by preoperative treatment and radicality of the resection. Patients who were re-irradiated had a similar outcome compared to patients, who were radiotherapy naive and could undergo full-course treatment, except the chance of local re-recurrence was higher for re-irradiated patients. Waiting-time between preoperative radiotherapy and IOERT was inversely correlated with the chance of local re-recurrence, and positively correlated with the chance of a R0 resection. CONCLUSIONS: R0 resection is the most important factor influencing oncologic parameters in treatment of LRRC. Preoperative (chemo)-radiotherapy increases the chance of achieving radical resections and improves oncologic outcomes. Short waiting-times between preoperative treatment and IOERT improves the effectiveness of IOERT to reduce the chance of a local re-recurrence.

Outcomes following surgery without radiotherapy for rectal cancer.

BACKGROUND: This study determined survival and recurrence rates following curative resection of rectal cancer without radiotherapy. METHODS: This was a retrospective review of the Mayo Clinic database of patients with rectal cancer treated with curative intent using surgery alone from 1990 to 2006. Patients who received neoadjuvant chemotherapy or radiation therapy and those who had any postoperative radiotherapy were excluded. Details were collected from the database and patient records using a protocol approved by the institutional review board. RESULTS: Some 655 consecutive patients with rectal cancer treated with curative intent using surgery alone were identified; 397 had stage I disease, 125 stage II and 133 stage III. Four hundred and nine patients underwent anterior resection (AR) and 246 abdominoperineal resection (APR). Median follow-up was 62 months. The 5-year rate of local recurrence was 4·3 per cent, disease-free survival 90·0 per cent and cancer-specific survival 91·5 per cent. Stage-specific and all-stage disease-free survival did not differ significantly between AR and APR. The 5-year cumulative local recurrence rate was lower following AR than APR (3·6 versus 5·5 per cent; P = 0·321). There were only two patients with positive margins and type of operation was not significant on multivariable analysis. CONCLUSION: Well-performed, standardized APRs have similar local recurrence to AR. Radiation therapy may not confer much additional benefit.

Impact of endoscopic ultrasonography and physician specialty on the management of patients with esophagus cancer.

While endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) are the most accurate techniques for locoregional staging of esophageal cancer, little evidence exists that these innovations impact on clinical care. The objective on this study was to determine the frequency with which EUS and EUS-FNA alter the management of patients with localized esophageal cancer, and assess practice variation among specialists at a tertiary care center. Three gastroenterologists, three medical oncologists, three radiation oncologists and four thoracic surgeons were asked to independently report their management recommendations as the anonymized staging information of 50 prospectively enrolled patients from another study were sequentially disclosed on-line. Compared to initial management recommendations, that were based upon history, physical examination, upper endoscopy and CT scan results, EUS prompted a change in management 24% (95% CI: 12-36%) of the time; usually to a more resource-intensive approach (71%), for example from recommending palliation to recommending neoadjuvant chemoradiation therapy. EUS-FNA plus cytology results altered management an additional 8% (95% CI: 6-15%) of the time. Agreement between specialists ranged from fair (intraclass correlation [ICC=0.32) to substantial (ICC=0.65); improving with additional information. Among specialists, agreement was greatest for patients with stage I disease. EUS and EUS-FNA changed patient management the most for patients with stages IIA, IIB or III disease. EUS, with or without FNA, significantly impacts the management of patients with localized esophageal cancer. With respect to the optimal treatment for each patient, agreement among physicians incrementally increases with endoscopic ultrasound results. Specialty training appears to influence therapeutic decision-making behavior.

Intraoperative radiotherapy for treatment of locally advanced and recurrent esophageal and gastric adenocarcinomas.

Intraoperative radiotherapy (IORT) allows delivery of radiotherapy doses in excess of those typically deliverable with conventional external beam radiotherapy. IORT has potential utility in clinical situations, such as treatment of esophageal and gastric malignancies, in which the radiation tolerance of normal organs limits the dose that can be given with conventional radiotherapy techniques. We reviewed the records of 50 patients who received IORT for locally advanced primary or recurrent gastric or esophageal adenocarcinomas deemed unresectable for cure. IORT was given as a single fraction of electron beam radiotherapy (10-25 Gy) after maximal tumor resection: R0 in 42%, R1 in 46%, and R2 in 12%. Forty-eight patients also received external beam radiotherapy (8-55 Gy), 46 received radiosensitizing chemotherapy, and nine received systemic chemotherapy after radiotherapy. Outcomes were estimated with Kaplan-Meier analysis. Median survival was 1.6 years. Overall survival at 1, 2, and 3 years was 70%, 40%, and 27%. Of 42 patients who died, 37 died from cancer progression and three from multifactorial treatment toxicity. Median survival for patients with recurrent disease versus primary disease was 3.0 years versus 1.3 years (P < 0.05), with a delay of metastatic failure in patients with recurrent tumors (P = 0.06). At 3 years, distant metastatic failure was 79%, local failure was 10%, and regional failure was 15%. IORT for locally advanced primary or recurrent gastric malignancies effectively decreases the risk of local failure. For patients with isolated local recurrences, IORT may be effective salvage therapy. However, more effective systemic therapy is needed as a component of treatment.

Sphincter-preserving radiation therapy for rectal cancer: a simulation study using three-dimensional computerized technology.

BACKGROUND: The acquisition of detailed computerized tomography (CT) imaging at the time of simulation, along with three-dimensional (3D) treatment planning software has been integrated with radiation delivery hardware to create the modality known as 3D conformal radiotherapy (3DXRT). This approach provides, in theory, a means to selectively subtract the anal sphincter from the high-dose field of irradiation in patients with stage II and III adenocarcinomas of the mid-rectum scheduled for low anterior resection (LAR). HYPOTHESIS: Implementation of 3DXRT with sphincter blocking may be a feasible strategy to reduce the dose of radiation distributed to the anal canal without reduction in the dose distribution to the gross tumour volume (GTV) plus adequate margins. METHODS: Pretreatment simulation CT scans of 10 patients with rectal cancers located between 5 and 10 cm from the anal verge were retrieved from a computerized database. Radiation oncologists and colorectal surgeons defined the contours of the GTV and the anal sphincter, respectively, on successive CT scan slices. These contours provided the volumetric data required to quantify dose distribution and compute dose-volume histograms. The standard mode of pelvic irradiation planned with CT simulation was compared with a 'virtual CT simulation' approach, in which a sphincter block was added to the protocol. RESULTS: The mean distance of tumours from the anal verge was 6.3 cm. In the virtual simulation treatment plan, a 2-cm margin separated the sphincter block from the lower limit of the GTV. The mean volume of the anal sphincter was 16.1 +/- 3.5 cm(3). The dose distributed to the GTV in the real plan and in the virtual simulated block plan were 51.7 +/- 1.4 and 51.6 +/- 1.4 Gy respectively (P = 0.85). By comparison the mean dose distributed to the anal sphincter was dramatically reduced by using a sphincter block (33.2 +/- 12 Gy vs 6.4 +/- 4.1 Gy, P < 0.001). CONCLUSION: During a course of radiotherapy for most low- or mid-rectal cancers, the anal canal is included within the field of irradiation with a mean dose distribution to the sphincter of 33 Gy. Evaluation of 3DXRT with full sphincter block (mid-rectum) and partial sphincter block (distal rectum) is a feasible strategy to decrease the volume of anal sphincter carried to full dose without reduction in dose to the GTV. This approach, by minimizing treatment-induced damage to the anal sphincter, might improve functional outcome of LAR.

Long-term follow-up of radical retropubic prostatectomy for prostate cancer.

OBJECTIVES: The ultimate outcome of patients after radical prostatectomy is often predicted from statistical projections of short-term follow-up. Only actual long-term follow-up can demonstrate true outcome. METHODS: One hundred thirty-one patients underwent retropubic prostatectomy for clinically organ confined prostate cancer and have been followed for a minimum of 22.5 years. Preoperatively, all but 12 had clinically palpable cancer. RESULTS: Overall survival in these patients was similar to an age-matched population, with 65% alive at 15 years, and 23% alive at 25 years. Thirty-seven percent of the patients recurred and 24% of all the patients died of prostate cancer. For patients with pathologically organ confined disease, 27% recurred, while those with extension outside the gland or positive nodes had an 83% recurrence rate. Although, the median time to recurrence was 7 years, recurrences occurred at a steady-state throughout the length of follow-up. Patients with higher grade tumors, even if organ confined, were significantly more likely to recur. CONCLUSIONS: In a cohort of patients treated with radical prostatectomy for predominantly palpable disease, long-term follow-up (79% deceased) reveals that 37% will recur and 24% will die of prostate cancer. Almost half the recurrences occurred after 10 years, indicating that reports with shorter follow-up will underestimate the recurrence rate.

Intraoperative irradiation for locally recurrent colorectal cancer in previously irradiated patients.

PURPOSE: Information in the literature regarding salvage treatment for patients with locally recurrent colorectal cancer who have previously been treated with high or moderate dose external beam irradiation (EBRT) is scarce. A retrospective review was therefore performed in our institution to determine disease control, survival, and tolerance in patients treated aggressively with surgical resection and intraoperative electron irradiation (IOERT) +/- additional EBRT and chemotherapy. METHODS AND MATERIALS: From 1981 through 1994, 51 previously irradiated patients with recurrent locally advanced colorectal cancer without evidence of distant metastatic disease were treated at Mayo Clinic Rochester with surgical resection and IOERT +/- additional EBRT. An attempt was made to achieve a gross total resection before IOERT if it could be safely accomplished. The median IOERT dose was 20 Gy (range, 10--30 Gy). Thirty-seven patients received additional EBRT either pre- or postoperatively with doses ranging from 5 to 50.4 Gy (median 25.2 Gy). Twenty patients received 5-fluorouracil +/- leucovorin during EBRT. Three patients received additional cycles of 5-fluorouracil +/- leucovorin as maintenance chemotherapy. RESULTS: Thirty males and 21 females with a median age of 55 years (range 31--73 years) were treated. Thirty-four patients have died; the median follow-up in surviving patients is 21 months. The median, 2-yr, and 5-yr actuarial overall survivals are 23 months, 48% and 12%, respectively. The 2-yr actuarial central control (within IOERT field) is 72%. Local control at 2 years has been maintained in 60% of patients. There is a trend toward improved local control in patients who received > or =30 Gy EBRT in addition to IOERT as compared to those who received no EBRT or <30 Gy with 2-yr local control rates of 81% vs. 54%. Distant metastatic disease has developed in 25 patients, and the actuarial rate of distant progression at 2 and 4 years is 56% and 76%, respectively. Peripheral neuropathy was the main IOERT-related toxicity; 16 (32%) patients developed neuropathies (7 mild, 5 moderate, 4 severe). Ureteral narrowing or obstruction occurred in seven patients. All but one patient with neuropathy or ureter fibrosis received IOERT doses > or =20 Gy. CONCLUSION: Long-term local control can be obtained in a substantial proportion of patients with aggressive combined modality therapy, but long-term survival is poor due to the high rate of distant metastasis. Re-irradiation with EBRT in addition to IOERT appears to improve local control. Strategies to improve survival in these poor-risk patients may include the more routine use of conventional systemic chemotherapy or the addition of novel systemic therapies.

Treatment of cholangiocarcinoma complicating primary sclerosing cholangitis: the Mayo Clinic experience.

OBJECTIVES: The aims of this retrospective study were to assess the frequency with which we used different treatment modalities for patients with primary sclerosing cholangitis (PSC) and cholangiocellular carcinoma (CCA). METHODS: A total of 41 patients with known CCA complicating PSC with a median age of 49 yr (range, 27-75 yr) were identified from a group of 1009 patients (4%) with PSC seen over 10 yr at the Mayo Clinic. RESULTS: These patients received mainly five forms of treatment: 10 patients were treated with radiation therapy (RT) with or without 5-fluorouracil (5-FU) (seven with palliative and three with curative intent), nine with stent placement for cholestasis, 12 with conservative treatment, four with surgical resection (one of four received RT and 5-FU), and three patients with orthotopic liver transplantation and RT, with or without 5-FU. One patient was treated with 5-FU alone, one with photodynamic therapy, and one patient with somatostatin analog. A total of 36 patients died, whereas four (10%) patients survived (two with surgical resection, one with orthotopic liver transplantation and RT, and one with stent placement) during a median follow-up of 5.5 months (range, 1-75 months). One patient was lost to follow-up. CONCLUSIONS: In highly selective cases, resective surgery seems to be of benefit in PSC patients with CCA. However, these therapies are rarely applied to these patients because of the advanced nature of the disease at the time of diagnosis. Efforts should be directed at earlier identification of potential surgical candidates.

Low-risk corpus cancer: is lymphadenectomy or radiotherapy necessary?

OBJECTIVE: The objective of this study was to find readily ascertainable intraoperative pathologic indicators that would discriminate a subgroup of early corpus cancers that would not require lymphadenectomy or adjuvant radiotherapy. STUDY DESIGN: Between 1984 and 1993, a total of 328 patients with endometrioid corpus cancer, grade 1 or 2 tumor, myometrial invasion < or =50%, and no intraoperative evidence of macroscopic extrauterine spread were treated surgically. Pelvic lymphadenectomy was performed in 187 cases (57%), and nodes were positive in nine cases (5%). Adjuvant radiotherapy was administered to 65 patients (20%). Median follow-up was 88 months. RESULTS: The 5-year overall cancer-related and recurrence-free survivals were 97% and 96%, respectively. Primary tumor diameter and lymphatic or vascular invasion significantly affected longevity. No patient with tumor diameter < or =2 cm had positive lymph nodes or died of disease. CONCLUSION: Patients who have International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid corpus cancer with greatest surface dimension < or =2 cm, myometrial invasion < or =50%, and no intraoperative evidence of macroscopic disease can be treated optimally with hysterectomy only.

Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma.

Orthotopic liver transplantation (OLT) alone for unresectable cholangiocarcinoma is often associated with early disease relapse and limited survival. Because of these discouraging results, most programs have abandoned OLT for cholangiocarcinoma. However, a small percentage of patients have achieved prolonged survival after OLT, suggesting that adjuvant approaches could perhaps improve the survival outcome. Based on these concepts, a protocol was developed at the Mayo Clinic using preoperative irradiation and chemotherapy for patients with cholangiocarcinoma. We report our initial results with this pilot experience. Patients with unresectable cholangiocarcinoma above the cystic duct without intrahepatic or extrahepatic metastases were eligible. Patients initially received external-beam irradiation plus bolus fluorouracil (5-FU), followed by brachytherapy with iridium and concomitant protracted venous infusion of 5-FU. 5-FU was then administered continuously through an ambulatory infusion pump until OLT. After irradiation, patients underwent an exploratory laparotomy to exclude metastatic disease. To date, 19 patients have been enrolled onto the study and have been treated with irradiation. Eight patients did not go on to OLT because of the presence of metastasis at the time of exploratory laparotomy (n = 6), subsequent development of malignant ascites (n = 1), or death from intrahepatic biliary sepsis (n = 1). Eleven patients completed the protocol with successful OLT. Except for 1 patient, all had early-stage disease (stages I and II) in the explanted liver. All patients who underwent OLT are alive, 3 patients are at risk at 12 months or less, and the remaining 8 patients have a median follow-up of 44 months (range, 17 to 83 months; 7 of 9 patients > 36 months). Only 1 patient developed tumor relapse. OLT in combination with preoperative irradiation and chemotherapy is associated with prolonged disease-free and overall survival in highly selected patients with early-stage cholangiocarcinoma.

Treatment of extraprostatic cancer in clinically organ-confined prostate cancer by permanent interstitial brachytherapy: is extraprostatic seed placement necessary?

PURPOSE: Successful treatment with ultrasound-guided transperineal interstitial permanent prostate brachytherapy (TIPPB) relies on effective radiation coverage of intraprostatic and clinically occult extraprostatic cancer. This study examines prostatectomy findings as they relate to treatment of extraprostatic extension (EPE) of cancer and TIPPB techniques and dosimetry. MATERIALS AND METHODS: A total of 313 prostatectomy specimens from patients with clinical tumor classification T1-T2b adenocarcinomas, serum prostate-specific antigen <20 ng/mL, and Gleason score <8 were whole mounted and evaluated for intraprostatic cancer volume and extraprostatic radial distance, area of perforation, and cancer density. From these data, extraprostatic cancer volume is calculated and used to estimate extraprostatic tumor control probabilities using the linear quadratic radiobiological model and Poisson statistics. TIPPB dose-gradient characteristics at the prostate periphery are examined. RESULTS: Intraprostatic cancer volume ranges from 0 to 38 cc, whereas extraprostatic cancer volume ranges from 0 to 4.6 cc (mean 0.06 cc). The radial distance of EPE ranges from 0 to 4.4 mm (mean 0.18 mm). The ratio of extraprostatic to intraprostatic cancer volume ranges from 0% to 18% (mean 0.4%). CONCLUSIONS: Only small amounts of clinically occult extraprostatic cancer were identified in the majority of specimens with EPE. Tumor control probability calculations suggest that this volume of cancer may be treated effectively with TIPPB. Treatment of this cancer possibly is achieved with an intraprostatic implant, but treatment of all cancers identified in this study suggests that some extraprostatic seed placement is desirable.

Results of irradiation or chemoirradiation following resection of gastric adenocarcinoma.

PURPOSE: To evaluate the results of postoperative irradiation +/- chemotherapy for carcinoma of the stomach and gastroesophageal junction. METHODS AND MATERIALS: The records of 63 patients who underwent resection for stomach cancer were retrospectively reviewed. Twenty-five patients had complete resection with no residual disease but with high-risk factors for relapse. Twenty-eight had microscopic residual and 10 had gross residual disease. Doses of irradiation ranged from 39.6 to 59.4 Gy with a median dose of 50.4 Gy in 1.8 Gy fractions. Fifty-three of the 63 (84%) patients received 5-fluorouracil (5-FU)-based chemotherapy. RESULTS: The median duration of survival was 19.3 months for patients with no residual disease, 16.7 months for those with microscopic residual disease, and 9.2 months for those with gross residual disease (p = 0.01). The amount of residual disease also significantly impacted locoregional control (p = 0.04). Patients with linitis plastica did significantly worse in terms of survival, locoregional control, and distant control than those without linitis plastica. The use of 4 or more irradiation fields was associated with a significant decrease in the rate of Grade 4 or 5 toxicity when compared to the patients treated with 2 fields (p = 0.05). CONCLUSIONS: There was a significant association between survival and extent of residual disease after resection as well as the presence of linitis plastica. Distant failures are common and effective systemic therapy will be necessary to improve outcome. The toxicity of combined modality treatment appears to be reduced by using greater than 2 irradiation fields.

Results of irradiation or chemoirradiation for primary unresectable, locally recurrent, or grossly incomplete resection of gastric adenocarcinoma.

OBJECTIVE: To evaluate the results of irradiation +/- chemotherapy for patients with unresectable gastric carcinoma. MATERIALS AND METHODS: The records of 60 patients with a gastric or gastroesophageal junction adenocarcinoma and a locally advanced unresectable primary (n = 28), a local or regional recurrence (n = 21), or gross residual disease following incomplete resection (n = 11) were retrospectively reviewed. Patients were treated with external beam irradiation (EBRT) alone or external beam plus intraoperative irradiation (IOERT), and 55 of the 60 (92%) patients received 5-FU based chemotherapy. RESULTS: The median survival for the entire cohort was 11.6 months. There was no significant difference in median survival between each of the three treatment groups. In examining the extent of disease there was a significant difference in survival based on the number of sites involved. Nine patients with disease limited to a single non-nodal site appeared to represent a favorable subgroup compared to the rest of the patients (median survival of 21.8 months vs. 10.2 months,p = 0.03). In the patients with recurrent disease, the number of sites involved (p = 0.05), and total dose adding external beam dose to IOERT dose (> 54 Gy vs. < or =54 Gy, p = 0.06) were of borderline significance in regard to survival. CONCLUSIONS: In patients with either primary unresectable, locally or regionally recurrent, or incompletely resected gastric carcinoma, the overall survival is similar, and related to the extent of disease based on the number of regional sites involved. The patients with a single non-nodal site of disease represent a favorable subgroup and patients with recurrent disease may benefit from total irradiation doses > 54 Gy.

Conformal irradiation for hepatobiliary malignancies.

The term 'conformal irradiation' is usually used to describe the delivery of sophisticated high dose external beam irradiation (EBRT) with the aid of 3-D treatment planning and the option of both coplanar and non-coplanar beams. Data will be presented from the University of Michigan which suggest that conformal high dose EBRT (48-72.6 Gy) can be used for intrahepatic cancers, both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC), to potentially increase local control and survival over what would be expected with lower dose EBRT. For purpose of this discussion, the term conformal irradiation will be expanded to include other techniques which conform the high dose irradiation boost volume in close proximity to unresected tumor or positive margins of resection. Data will be presented from series which utilize transcatheter iridium and intraoperative electron irradiation (IOERT) supplements to EBRT +/- concomitant chemotherapy. Each method intensifies treatment in an attempt to improve local control and survival.

Future role of radiotherapy as a component of treatment in biliopancreatic cancers.

For resected and unresectable pancreas cancers, data will be summarized from both adjuvant and locally unresectable pancreas cancer series (EBRT +/- IOERT) to demonstrate the justification of continuing to utilize chemo-irradiation as a component of treatment. The resultant improvements in local control with combined modality treatment, however, achieve only minimal improvements in survival in view of the high incidence of abdominal relapse (liver and peritoneal). Further improvement in survival may necessitate regional approaches for chemotherapy or may await advances in gene therapy. For locally unresectable and resected but residual bile duct malignancies, chemoirradiation appears to enhance tumor control and survival. Dose intensification of both modalities may be useful in improving disease control and survival. After chemoirradiation, the addition of liver transplant, in carefully selected patients who are unresectable with standard resection, may further enhance disease control and survival over what would be expected with either approach in isolation.

Radiation therapy for histologically confirmed primary central nervous system germinoma.

PURPOSE: To evaluate survival and patterns of recurrence in patients with primary central nervous system germinoma treated with radiation therapy. METHODS AND MATERIALS: Data regarding 48 patients with histologically confirmed, primary central nervous system germinoma were reviewed. All had been operated on at the Mayo Clinic between the years 1935 and 1993. Thirty-two patients (67%) were treated since 1973. The study group included 39 males and 9 females, with a median age at diagnosis of 17 years (range, 6-42 years). Twelve patients (25%) were treated with craniospinal axis irradiation, 11 (23%) received whole-brain irradiation without spinal axis irradiation, and 24 (50%) underwent partial-brain irradiation. Treatment volumes were unknown in one patient. The median dose to the primary tumor was 44.00 Gy (range, 7.44-59.40 Gy). The median follow-up was 5.5 years (range, 4 months to 37 years). RESULTS: Actuarial 5-year and 10-year survival for the entire study group of patients was 80%. There was a trend toward improved survival in patients treated after 1973 (introduction of computed tomography) with 5-year and 10-year survival of 91% vs. 63% in prior years (p = 0.07). For the group of 31 patients treated since 1973 with known treatment volumes, the spinal axis failure rate at 5 years was 49% for patients treated with partial brain fields (11 patients) vs. 0% for those having undergone whole brain (10 patients) or craniospinal axis (10 patients) irradiation (p = 0.007). The rate of brain failure was also significantly higher in patients receiving less than whole-brain irradiation; at 5 years, 45% of the patients treated with partial-brain fields had intracranial recurrence of disease compared to 6 % of patients treated with craniospinal axis or whole-brain irradiation (p = 0.01). Among the 32 modern era patients, the rate of brain failure was higher in patients who received doses less than 40 Gy (median dose, 48.55 Gy; range, 30.60-59.40 Gy) to the primary tumor (5-year brain failure rate 52% vs. 11%, p = 0.002). CONCLUSION: The long-term survival of patients with histologically proven CNS germinoma treated with radiation is excellent. Whole-brain or craniospinal axis irradiation appears to result in fewer spine and brain failures than does partial-brain irradiation. Furthermore, the administration of doses greater than 40 Gy to the primary tumor is associated with better local control.

Central neurocytomas.

BACKGROUND: This analysis was performed to examine the outcome of patients with histologically confirmed central neurocytomas. METHODS: Thirty-two patients with histologically confirmed central neurocytomas were evaluated retrospectively. Patients were treated with various combinations of surgery, chemotherapy, and radiotherapy (RT). Follow-up ranged from 2.3 to 15.3 years (median, 4.7 years). RESULTS: The overall 5-year survival and local control rates were 81% and 79%, respectively. No patient developed metastases. The 5-year local control rate was 70% for patients undergoing subtotal resection (STR) and 100% for those undergoing gross total resection (GTR) (P = 0.08). The 5-year survival rate was 77% for patients undergoing STR and 90% for those undergoing GTR (P = 0.44). The effect of RT was evaluated for patients undergoing STR. The 5-year local control rate was 100% for patients who received RT after STR compared with 50% for those who did not (P = 0.02). The 5-year survival rate was 88% for patients who received RT after STR compared with 71% for those who did not (P = 0.3). Three patients received salvage RT for local progression after resection. All were alive and free of disease 1 to 6 years after RT. CONCLUSIONS: GTR results in a very high likelihood of local control and survival. Postoperative RT appears to improve local control rates significantly for patients who have undergone STR. The overall prognosis of patients with central neurocytomas is quite favorable, with an actuarial 5-year survival rate of 81%.

A multiple prognostic index predictive of disease outcome after irradiation for clinically localized prostate carcinoma.

BACKGROUND: This investigation was conducted to identify independent pretherapy disease-related factors associated with disease outcome in patients with clinically localized carcinoma of the prostate (CaP) and to develop models that incorporated relevant covariates for estimating the risk of disease relapse after irradiation (RT). METHODS: The outcome of 500 patients treated only with RT between March 1987 and June 1993 for clinical Stages T1-4N0,XM0 CaP was evaluated. The risk of disease relapse as a function of individual prognostic variables, and combinations thereof, was determined using logistic regression. RESULTS: With a median follow-up of 43 months (range, 4-103 months), 69 patients (14%) had clinical evidence of local recurrence (27 patients), regional lymph node relapse (4 patients), or metastatic relapse (38 patients) within 5 years of RT. Forty additional patients (8%) had biochemical relapse based solely on the post-RT serum prostate specific antigen (PSA) profile. Clinical tumor stage (P = 0.0006), Gleason score (P = 0.001) of the diagnostic biopsy specimen, and pretherapy PSA (P < 0.0001) were associated with disease relapse. The risk of any relapse within 5 years of RT was determined and graphically displayed as risk estimate plots for combinations of these pretherapy prognostic variables. CONCLUSIONS: The combination of pretherapy clinical tumor (T) stage, Gleason score, and PSA level can be used to obtain improved estimates of the risk for disease relapse in patients treated solely with RT for clinically localized CaP. Risk estimate plots of this type may facilitate exchange of therapeutic outcome information, be instrumental in pretherapy decision-making for the new patient with this condition, and aid in the selection of patients for future studies.

The treatment of locally advanced colon cancer.

PURPOSE: The results of therapy for 103 patients with locally advanced colon cancer who received radiotherapy were analyzed to determine the outcome and tolerance of therapy. METHODS AND MATERIALS: Between 1974 and 1994, 103 patients received radiotherapy and maximal resection of locally advanced colon cancers. Following resection, 50 patients had no residual disease, 18 patients had microscopic residual disease, and 35 patients had gross residual disease. External beam radiotherapy was initiated 1 to 4 months following resection except in two patients who received preoperative radiotherapy. Treatment was delivered to the tumor bed and adjacent lymph nodes using 4 to 18 MV X-rays with doses ranging from 16.2 to 60 Gy. Intraoperative electron radiotherapy (IOERT) was also administered to 11 of the patients with doses ranging from 10 to 20 Gy. Chemotherapy was administered to 77 patients. Follow-up in survivors ranged from 0.5 to 17 years (median: 5.8 years). RESULTS: The 5-year actuarial local failure rate was 10% for patients with no residual disease, 54% for patients with microscopic residual disease, and 79% for patients with gross residual disease (p < 0.0001). For patients with residual disease, local failure occurred in 11% of patients receiving IOERT compared with 82% of patients receiving only external beam therapy (p = 0.02). The 5-year actuarial survival rate was 66% for patients with no residual disease, 47% for patients with microscopic residual disease, and 23% for patients with gross residual disease (p = 0.0009). The 5-year survival rate in patients with residual disease was 76% for patients receiving IOERT and 26% for patients receiving external beam therapy alone (p = 0.04). CONCLUSIONS: Patients with locally advanced colon cancer who have had a complete resection have a high probability of local control after external beam irradiation +/- 5 fluorouracil (5FU)-based systemic therapy. The toxicity of therapy can be minimized with attention to treatment technique and dose. Local control and survival rates in patients with residual disease who received IOERT appear to be significantly greater than for those patients who received external beam radiotherapy therapy alone.