The impact of radiation therapy in patients with diffuse large B-cell lymphoma with positive post-chemotherapy FDG-PET or gallium-67 scans.

BACKGROUND: 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (PET) and gallium-67 citrate (gallium) response after chemotherapy are powerful prognostic factors in diffuse large B-cell lymphoma (DLBCL). However, clinical outcomes when consolidation radiation therapy (RT) is administered are less defined. PATIENTS AND METHODS: We reviewed 99 patients diagnosed with DLBCL from 1996 to 2007 at Duke University who had a post-chemotherapy response assessment with either PET or gallium and who subsequently received consolidation RT. Clinical outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Median follow-up was 4.4 years. Stage distribution was I-II in 70% and III-IV in 30%. Chemotherapy was R-CHOP or CHOP in 88%. Median RT dose was 30 Gy. Post-chemotherapy PET (n = 79) or gallium (n = 20) was positive in 21 of 99 patients and negative in 78 of 99 patients. Five-year in-field control was 95% with a negative PET/gallium scan versus 71% with a positive scan (P < 0.01). Five-year event-free survival (EFS; 83% versus 65%, P = 0.04) and overall survival (89% versus 73%, P = 0.04) were also significantly better when the post-chemotherapy PET/gallium was negative. CONCLUSIONS: A positive PET/gallium scan after chemotherapy is associated with an increased risk of local failure and death. Consolidation RT, however, still results in long-term EFS in 65% of patients.

Timing and patterns of recurrences and deaths from prostate cancer following adjuvant pelvic radiotherapy for pathologic stage T3/4 adenocarcinoma of the prostate.

To determine the timing and patterns of late recurrence after radical prostatectomy (RP) alone or RP plus adjuvant radiotherapy (RT). Between 1970 and 1983, 159 patients underwent RP for newly diagnosed adenocarcinoma of the prostate and were found to have positive surgical margins, extracapsular extension and/or seminal vesicle invasion. Of these, 46 received adjuvant RT and 113 did not. The RT group generally received 45-50 Gy to the whole pelvis, then a boost to the prostate bed (total dose of 55-65 Gy). In the RP group, 62% received neoadjuvant/adjuvant androgen deprivation vs 17% in the RT group. Patients were analyzed with respect to timing and patterns of failure. Only one patient was lost to follow-up. The median follow-up for surviving patients was nearly 20 years. The median time to failure in the surgery group was 7.5 vs 14.7 years in the RT group (P=0.1). Late recurrences were less common in the surgery group than the RT group (9 and 1% at 10 and 15 years, respectively vs 17 and 9%). In contrast to recurrences, nearly half of deaths from prostate cancer occurred more than 10 years after treatment. Deaths from prostate cancer represented 55% of all deaths in these patients. Recurrences beyond 10 years after RP in this group of patients were relatively uncommon. Despite its long natural history, death from prostate cancer was the most common cause of mortality in this population with locally advanced tumors, reflecting the need for more effective therapy.

Radiation therapy and hyperthermia improve the oxygenation of human soft tissue sarcomas.

The adverse prognostic impact of tumor hypoxia has been demonstrated in human malignancy. We report the effects of radiotherapy and hyperthermia (HT) on soft tissue sarcoma oxygenation and the relationship between treatment-induced changes in oxygenation and clinical treatment outcome. Patients receiving preoperative radiotherapy and HT underwent tumor oxygenation measurement pretreatment after the start of radiation/pre-HT and one day after the first HT treatment. The magnitude of improvement in tumor oxygenation after the first HT fraction relative to pretreatment baseline was positively correlated with the amount of necrosis seen in the resection specimen. Patients with <90% resection specimen necrosis experienced longer disease-free survival than those with > or = 90% necrosis. Increasing levels of tumor hypoxia were also correlated with diminished metabolic status as measured by P-31 magnetic resonance spectroscopy.

Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma.

This study was performed to explore the relationship between tumor oxygenation and treatment outcome in human soft tissue sarcoma. Twenty-two patients with nonmestastatic, high-grade, soft tissue sarcomas underwent preoperative irradiation and hyperthermia and pretreatment measurement of tumor oxygenation. The 18-month actuarial disease-free survival was 70% for patients with tumor median oxygen pressure (pO2) values of >10 mm Hg but only 35% for those with median pO2 values of <10 mm Hg (P=0.01). There were eight treatment failures; the first site of recurrence was lung in all patients. Median pO2 was 7.5 mm Hg for metastasizing tumors versus 20 mm Hg for nonmetastasizing tumors (P=0.03). Potential mechanisms and implications for clinical trial design are discussed.

Prognostic importance of restaging gallium scans following induction chemotherapy for advanced Hodgkin's disease.

PURPOSE: This study was intended to assess the ability of restaging gallium scanning to distinguish between patients with residual radiographic abnormalities who still have active Hodgkin's disease (HD) and those who are truly complete responders. Early identification of the former patients might increase the success of secondary salvage therapy. MATERIALS AND METHODS: The charts of all patients with advanced HD treated at Duke University Medical Center during the years 1983 to 1991 who underwent gallium scanning were reviewed. Thirty-three patients were identified who had gallium scans performed as part of restaging following induction combination chemotherapy; no patient had other signs or symptoms of active or progressive HD. RESULTS: Thirteen of 33 patients had positive restaging gallium scans; 20 patients had negative scans. The 4-year actuarial relapse-free survival (RFS) rate was 75% for patients with negative restaging gallium scans compared with 8% for those with positive restaging scans (P < .001). The 4-year actuarial overall survival (OS) rate was 100% for those with negative scans compared with 51% for gallium-positive patients (P = .001). Twenty-four patients had residual chest x-ray or computed tomographic scan abnormalities. Calculated negative and positive predictive values for gallium scanning are 92% and 90%, respectively, compared with values of 48% and 83% for computed tomographic scanning. CONCLUSION: Restaging gallium scans separate complete responders from induction failures with a high degree of accuracy. Gallium scanning is clearly superior to computed tomography in this regard. Patients with advanced HD who have positive restaging gallium scans after induction chemotherapy should be classified as induction failures and are highly unlikely to be cured with involved-field low-dose radiotherapy.

Second solid malignancies after combined modality therapy for Hodgkin's disease.

PURPOSE: To determine the actuarial incidence (AI) and relative risk (RR) of second solid malignancies (SSM; solid tumors and non-Hodgkin's lymphoma) in patients with Hodgkin's disease who were treated with chemotherapy and adjuvant, low-dose radiation (combined modality therapy; CMT). PATIENTS AND METHODS: From 1969 to 1983, 102 patients with previously untreated advanced Hodgkin's disease (group A) and 81 patients with recurrent disease after radiation (group B) were treated with CMT. Patients were observed for the development of solid tumors (ST) and non-Hodgkin's lymphoma (NHL), and the AI and RR were calculated. RESULTS: Nearly half of the patients entering remission were observed for greater than 15 years. At 20 years, the AI for SSM was 12% in group A versus 41% in group B (P = .009). The overall RR for developing a ST in group A was 1.88 (not significant) versus 8.84 in group B (95% confidence interval, 5.3 to 15.4). The difference in the RR between groups A and B was significant (P < .001). The RR for developing NHL was significantly increased in both groups, but the difference between groups was not significant. CONCLUSION: Previously untreated patients with advanced disease who were treated with CMT (group A) had a modest but not significant increase in the RR of ST; however, patients treated with CMT for recurrent disease (group B) had a highly significant increase in the RR of ST. Possible explanations for the increase in ST in group B include more cumulative radiation or a greater carcinogenic effect of chemotherapy in previously irradiated patients, but it also is possible that the increase is due to a longer follow-up time.

Is axillary lymph node dissection indicated for early-stage breast cancer? A decision analysis.

PURPOSE: Axillary lymph node dissection (ALND) has been a standard procedure in the management of breast cancer. In a patient with a clinically negative axilla, ALND is performed primarily for staging purposes, to guide adjuvant treatment. Recently, the routine use of ALND has been questioned because the results of the procedure may not change the choice of adjuvant systemic therapy and/or the survival benefit of a change in adjuvant therapy would be small. We constructed a decision model to quantify the benefits of ALND for patients eligible for breast-conserving therapy. METHODS: Patients were grouped by age, tumor size, and estrogen receptor (ER) status. The model uses the Oxford overviews and three combined Cancer and Leukemia Group B studies. We assumed that patients who did not undergo ALND received axillary radiation therapy and that the two procedures are equally effective. All chemotherapy combinations were assumed to be equally efficacious. RESULTS: The largest benefits from ALND are seen in ER-positive women with small primary tumors who might not be candidates for adjuvant chemotherapy if their lymph nodes test negative. Virtually no benefit results in ER-negative women, almost all of whom would receive adjuvant chemotherapy. When adjusted for quality of life (QOL), ALND may have an overall negative impact. In general, the benefits of ALND increase with the expected severity of adjuvant therapy on QOL CONCLUSION: Our model quantifies the benefits of ALND and assists decision making by patients and physicians. The results suggest that the routine use of ALND in breast cancer patients should be reassessed and may not be necessary in many patients.

Combined modality therapy for advanced Hodgkin's disease: 15-year follow-up data.

From 1969 through 1982, 184 patients with advanced Hodgkin's disease (HD) were treated with combined modality therapy (CMT) at Yale University. The data were reanalyzed in November 1986, with a mean follow-up of 10 years. The patient population consisted of 102 newly diagnosed stages IIIB and IV patients, and 82 patients who had relapsed after initial radical radiotherapy. From 1969 through 1978, the treatment program was induction chemotherapy with nitrogen mustard, vincristine, vinblastine, procarbazine, and prednisone (MVVPP) for three cycles (6 months) followed by low-dose radiation (1,500 to 2,500 cGy) for patients who had achieved complete remission (CR), to all disease sites present before the onset of chemotherapy. From 1978 to 1982, selected "poor-risk" advanced-stage patients received nitrogen mustard, vincristine, procarbazine, prednisone plus Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), bleomycin, vinblastine, and dacarbazine (MOPP-ABVD) induction chemotherapy, while the remaining patients were randomized between MVVPP and MOPP. One hundred fifty-one patients have achieved CR (82%); 23 (15%) of these 151 have relapsed, with the remaining 128 patients in continuous CR. A total of 62 patients have died, 45 due to HD, and 17 due to other causes. Twelve of these 17 patients died of second malignancies. The 15-year actuarial survival of all patients is 54%. It is 71% if deaths due only to HD are considered. Within the overall group of advanced HD patients, age and multiple extranodal sites of involvement continue to constitute adverse risk factors. The three drug programs used were all equivalent. No improvement resulted from the use of MOPP-ABVD in the poor-risk patients. These results compare favorably with those recently published by the National Cancer Institute (NCI). CMT resulted in an approximate 20% improvement in survival with no increase in second malignancies when compared with chemotherapy alone.

Second neoplasms in patients with Hodgkin's disease following combined modality therapy--the Yale experience.

From 1969 to 1982, 183 patients with previously untreated stages IIIB and IV Hodgkin's disease and relapsing Hodgkin's disease after radiation therapy were treated with combination chemotherapy plus low-dose irradiation (CRT). One hundred fifty patients who achieved a complete response (CR) were analyzed for risk of developing a second neoplasm. Median follow-up has been 8.3 years. Actuarial survival of all patients is 74% at 10 years with a relapse-free survival of 68%. An additional 24 patients with stage IIIA disease were also treated with CRT. There were 22 CRs at risk who were analyzed. Median follow-up has been 3+ years with an actuarial survival of 90% at five years and a relapse-free survival of 83%. Second neoplasms have developed in 14 of 172 patients at risk: acute nonlymphocytic leukemia (ANLL; five patients); aggressive histology non-Hodgkin's lymphoma (NHL; three patients); and a variety of solid neoplasms (six patients). Time to second neoplasm diagnosis after initial treatment ranged from 12 to 141 months. Five patients were older than 40 years. At the time of diagnosis of the second malignancy, 11 patients were free of Hodgkin's disease (for 36 to 141 months) and three were receiving therapy for recurrent Hodgkin's disease. The 10-year actuarial risk (%) of developing ANLL was 5.9 +/- 2.8; for NHL, the risk was 3.5 +/- 2.4, and for solid neoplasms, 5.8 +/- 3.0. Our results suggest that combination chemotherapy plus low-dose irradiation does not appear to significantly increase the risk of developing second neoplasms above that already reported for combination chemotherapy when administered as either initial or salvage treatment of Hodgkin's disease.

Impact of consolidation radiotherapy in patients with advanced breast cancer treated with high-dose chemotherapy and autologous bone marrow rescue.

PURPOSE: To examine the impact of consolidation radiotherapy (RT) after high-dose chemotherapy with autologous bone marrow rescue (HDC) in patients with advanced breast cancer. PATIENTS AND METHODS: Between 1988 and 1994,425 patients with metastatic or recurrent breast cancer received doxorubicin, fluorouracil, and methotrexate (AFM) induction chemotherapy in a single-institution prospective trial. One hundred patients who achieved a complete response were randomized to receive HDC (cyclophosphamide, cisplatin, carmustine), with autologous bone marrow rescue immediately after AFM, or to observation, with HDC to be administered at next relapse. Seventy-four of the 100 became eligible for RT; 53 received consolidation RT (HDC RT+ and 21 did not (HDC RT-). The assignment of RT was not randomized. The RT+ and RT- groups were similar with regard to number of involved sites, the fraction of patients with only local-regional disease, age, and interval since initial diagnosis. Local control at previously involved sites and distant sites was assessed with extensive radiologic and clinical evaluations at the time of first failure or most recent follow-up. The impact of RT on failure patterns, event-free survival, and overall survival was evaluated. RESULTS: Sites of first failure were located exclusively at previously involved sites in 28% of RT+ patients versus 62% of RT- patients (P < .01). Event-free survival at 4 years was 31% and 21% in the RT+ and RT-groups, respectively (P = .02). Overall survival at 4 years was 30% and 16% in the RT+ and RT- groups, respectively (P = .20). CONCLUSION: Patients with advanced breast cancer who were treated with HDC without RT failed predominantly at the initial sites of disease. The addition of RT appeared to reduce the failure rate at initial disease sites and may improve event-free and overall survival. Our observations await verification in a trial in which assignment to RT is randomized.

Postmastectomy radiotherapy: toxicities and techniques to reduce them.

The role of locoregional radiation therapy after mastectomy is controversial. It reduces the risk of tumor relapse, improves breast cancer-specific survival and possibly overall survival, but has potential morbidity. This article reviews the technical aspects of postmastectomy radiation therapy and its associations with treatment-related morbidity. We consider common problems that arise in the technical setup of radiation fields. Adverse effects of postmastectomy radiation therapy may be reduced or prevented by careful radiation treatment planning.

Radiotherapy vs. hormonal therapy for the management of locally recurrent prostate cancer following radical prostatectomy.

Forty patients out of 273 who had undergone radical surgery for adenocarcinoma of the prostate at Duke University Medical Center between 1970 and 1983 developed palpable, biopsy-proven local recurrence without evidence of distant metastases. Of these 40 patients, 16 were treated with irradiation alone (Group I) and 16 patients were treated with hormonal therapy only (Group II). The remaining eight patients received either no therapy (4 patients) or both radiotherapy and hormonal therapy (4 patients) and are not further analyzed. Local control, as determined by palpation, was achieved in 14/16 patients in Group I versus only 7/16 patients in Group II (p less than 0.05). Subsequently, six patients in each group have relapsed, all with distant metastases. Thus, 8/16 patients in Group I remain alive without disease versus only 1/16 patients in Group II (p less than 0.05). There was no difference in survival between Groups I and II. No patient in either group has died free of disease. In Group I, 4/16 patients have died with cancer. Six of 16 in Group II have died with cancer. Severe complications occurred more frequently following irradiation compared to hormonal therapy. Irradiation appears to be superior to hormonal therapy in achieving local control and prolonging disease-free survival. Neither therapy conveys an advantage over the other in terms of survival. Thus, even if local control is achieved, distant failure may be an inevitable consequence of locally recurrent prostate cancer. Therefore, prevention of local recurrence after radical prostatectomy is of paramount importance. These findings support the use of adjuvant post-operative irradiation in patients at high risk for local recurrence.

Multivariate analysis of factors predicting local relapse after radical prostatectomy--possible indications for postoperative radiotherapy.

Between 1970 and 1983, 273 patients underwent radical surgery (radical prostatectomy--261, radical cystoprostatectomy--12) for newly diagnosed adenocarcinoma of the prostate at Duke University Medical Center and received no adjuvant radiotherapy. A total of 46 patients developed local recurrence. Forty developed local relapse only and six developed simultaneous local and distant failure. The crude local relapse rate was 17% (46/273). The actuarial local failure rate at 5, 10, and 15 years was 12%, 32%, and 35%, respectively. Univariate and multivariate analyses were performed to identify factors predictive of local relapse after radical surgery. Possible prognostic factors analyzed were: age, type of biopsy, use of adjuvant hormonal therapy, histologic grade, histologic involvement of seminal vesicles, positive surgical margins, clinical stage, and elevated acid phosphatase. Factors identified as significant predictors of local relapse by univariate analysis were: poorly differentiated histology (p = 0.0001), seminal vesicle involvement (p = 0.0009), and positive surgical margins (p = 0.0001). An elevated preoperative acid phosphatase was of borderline significance (p = 0.06). On multivariate analysis, poorly differentiated histology (p = 0.0007), positive margins (p = 0.0015), and elevated acid phosphatase (p = 0.0273) were significant predictors of local failure. Seminal vesicle involvement was no longer a significant predictor of local failure. However, on subsequent univariate and multivariate analyses, seminal vesicle involvement was the only significant predictor for the development of distant metastases (p = 0.0019, multivariate). Thus, patients with poorly differentiated tumors, positive surgical margins, or elevated preoperative acid phosphatase are at high risk for local relapse after radical prostatectomy. These patients should be included in future clinical trials studying the role of adjuvant radiotherapy after radical prostatectomy, or offered adjuvant radiotherapy if they cannot or will not participate in such trials.

Comparison of two repositioning devices used during radiation therapy for Hodgkin's disease.

PURPOSE: Patients irradiated for Hodgkin's disease are fixed in an immobilization cradle to improve repositioning. In the early 1990s, we changed our cradle system from a "short" upper torso cradle to an extended near-total body cradle that also includes the lower torso and thighs. In this study, we assess the impact of the extended cradle on the reproducibility of patient repositioning during irradiation of Hodgkin's disease. METHODS AND MATERIALS: A total of 782 port films of 56 patients treated immediately before and after the change-over were studied to assess positioning reproducibility. Patients treated prior to 1993 were positioned in the short cradle, while those treated 1993 and later were positioned in the extended cradle. All treatment were delivered via anterior and posterior fields and treatment areas above and below the diaphragm were considered separately and together. All treatment fields were simulated and the field shape was designed on anterior and posterior radiographs. Discrepancies in field placement between the simulation radiographs and subsequent port films were noted by a radiation oncologist and requests for position adjustment (both translational and rotational shifts) were noted. The number, magnitude, and direction of any physician-requested position adjustment on port films were retrospectively reviewed. For the purpose of scoring the frequency of field misplacements, when an adjustment was noted on two port films taken during the same treatment session (i.e., a left shift on both an anterior and a posterior port film), it was scored as only one event. A two-tailed chi-square test was used to compare the differences in requested shifts in the two patient groups. RESULTS: The study population consisted of 56 patients (31 short and 25 extended cradle) representing 92 treatment sites. A total of 782 port films representing 450 treatment setups were analyzed (292 above and 158 below the diaphragm). When all port films above the diaphragm (mostly mantle fields) are considered, position adjustments were requested in 13.4% (21 out of 157) of treatment setups with the upper torso cradle and in 5.9% (8 out of 135) of treatment setups with the extended cradle (p = 0.054). When all port films below the diaphragm (mostly paraaortic/spleen and pelvic fields) are considered, position adjustments were requested in 33.8% (27 out of 80) of treatment setups with the upper torso cradle and in 16.7 % (13 out of 78) of treatment setups with the extended cradle (p = 0.056). A reduction in the frequency of both translational and rotational adjustments were seen. When both treatment sites are combined, position adjustments were requested in 20.3% (48 out of 237) of treatment setups with the upper torso cradle and in 9.9% (21 out of 213) of treatment setups when the extended cradle was used (p = 0.0086). CONCLUSIONS: The extended cradle provides superior repositioning of patients undergoing radiation therapy for Hodgkin's disease. Differences observed in setup accuracy in this study underscore the importance of aggressive immobilization of patients with Hodgkin's disease. Increased accuracy of daily setup may provide an opportunity to improve the therapeutic ratio both by increased likelihood of tumor control and decreased risk of normal tissue complications.

Radiation techniques for the treatment of Hodgkin's disease with combined modality therapy or radiation alone.

This article reviews radiation techniques including field arrangements, anatomic borders, and doses for the treatment of Hodgkin's disease when radiotherapy is being used as the sole treatment and when it is part of a planned combined modality program with chemotherapy. We describe the techniques currently in use at Duke University Medical Center. Particular emphasis is placed on the evidence regarding the appropriate extent of the treatment field and the doses of radiation necessary to achieve local control. These issues assume increasing importance as we attempt to maintain high cure rates for Hodgkin's disease but lower the frequency of serious long-term complications.

Treatment selection for stage IIIA Hodgkin's disease patients.

Two treatment policies for the therapy of patients with Stage IIIA Hodgkin's disease are compared. From 1969-1976, 49 newly diagnosed and pathologically staged IIIA patients received total nodal irradiation (TNI) alone (no liver irradiation). Although actuarial survival was 80% at 5 years and 68% at 10 years, actuarial freedom from relapse was only 38% at 5 years. Accordingly, a new treatment policy was instituted in 1976. Patients with either CS IIIA disease, multiple splenic nodules, IIIA with a large mediastinal mass or III2, received combined modality therapy (combination chemotherapy and irradiation). All others received TNI. Thirty-six patients have been treated under the new program. The actuarial survival is 90% at 5 years and the relapse-free survival is 87%, suggesting the superiority of this approach.

Pretreatment oxygenation profiles of human soft tissue sarcomas.

PURPOSE: Tumor oxygenation is thought to influence the radiocurability of many malignancies. Advances in polarographic electrode technology have facilitated the in situ measurement of human tumor pO2. The optimal method of defining a "hypoxic" tumor is not known. Characterization of intra-tumor and intertumor pO2 heterogeneity could help with this process. This study was performed to evaluate pretreatment tumor oxygenation status and pO2 heterogeneity in patients with soft tissue sarcoma. METHODS AND MATERIALS: Nine patients with soft tissue sarcomas underwent pretreatment pO2 measurements with the Eppendorf pO2 histograph. Two grossly distinct anatomic sites within each tumor were measured in all but one patient; these were localized under computerized tomography guidance to ensure that all measurements were obtained from tumor tissue. Multiple probe tracks were studied at each site. Measurements were performed in resting, awake patients. RESULTS: A total of 1588 pO2 readings was obtained (mean = 176/patient). Measurement path lengths ranged from 22-36 mm. The average hypoxic fraction (pO2 < 5 mm Hg) was 29% (range 0-76%). Arterial pO2 was positively correlated with mean and median tumor pO2. Tumor hypoxic fraction increased with increasing tumor volume. Linear pO2 profiles and frequency histograms provided similar estimates of the extent of hypoxia in individual tumors. Marked variation in oxygenation existed both within and between individual tumors. The intertumor variation was greater than the intratumor variation. CONCLUSION: Radiobiologic hypoxia exists in human soft tissue sarcomas. The pO2 variation within individual tumors is less than the variation between tumors. Further study is necessary to identify the best parameter for defining tumor hypoxia and to discern the relationship between tumor pO2 and treatment outcome.

A practical and easy method to locate the first three internal mammary lymph node-bearing areas.

PURPOSE: To assess the distance from a clinically recognized anatomic landmark to the different costocondral interspaces in female patients to facilitate the design of radiation fields intended to include specific internal mammary nodal areas. METHODS AND MATERIALS: The distance from the suprasternal notch (SSN) to the caudal portion of the first through fourth interspace was measured on a computer display of the chest skeleton of 65 female patients with left-sided breast cancer. The relationship between these distances and bone size (sternal length and standing height) was assessed via linear regression. In 21 of the 65 patients where myocardial perfusion imaging of the heart was available, the relationship between the location of the 3rd costochondral interspace and the left ventricle was assessed. RESULTS: In 90% of patients (59/65), the first, second, third, and fourth interspace were within 5, 8.5, 11, and 14 cm of the SSN, respectively. The SSN-interspace distances did not correlate well with sternal length (r = 0.28) or standing height (r = 0.31). In 20 of 21 patients (95%), the third interspace "shadowed" the cephalad aspect of the left heart ventricle. Median "shadowing" was 3 cm (range 0.5-6 cm). CONCLUSION: The caudal portion of the third costochondral interspace is < or = 11 cm caudal to the SSN in 90% of patients. These measurements can be used to clinically design radiation therapy fields intended to treat the upper three interspaces. The distance from the SSN to the 1st through 4th interspaces is not related to sternal length or to standing height. In patients with left-sided breast cancer, radiation treatment fields designed to include the internal mammary lymph nodes in the upper three interspaces may incidentally include a portion of the heart.

Combined external beam irradiation and external regional hyperthermia for locally advanced adenocarcinoma of the prostate.

PURPOSE: To determine the safety and efficacy of combined external beam irradiation and external regional hyperthermia in the treatment of adenocarcinoma of the prostate. METHODS AND MATERIALS: From 1987 to 1994, 30 patients received combined external beam irradiation and external regional hyperthermia for locally advanced prostate cancer. The results of the 21 patients with newly diagnosed (n = 18) or locally recurrent (n = 3) adenocarcinoma are reported herein. No patient had evidence of distant metastases. Total radiotherapy doses of 65-70 Gy to the prostate were planned using a four-field box technique. Hyperthermia treatments were delivered using an annular phased array microwave device. The treatment goal was to achieve temperatures > or = 42 degrees C in all measured points within the prostate. RESULTS: Of the newly diagnosed patients, 16 out of 18 (89%) had T3 or T4 tumors, 11 out of 18 (61%) had Gleason scores of 7-9, and the mean pretreatment Prostate Specific Antigen (PSA) was 69 ng/ml. The median follow-up of all 21 patients was 36 months. None of the patients achieved the treatment goal of all intratumoral temperatures > or = 42 degrees C. The mean CEM 43 T90 was 2.34 min. The disease-free survival at 36 months is 25%; 12 out of 18 (67%) of the patients have relapsed. The only significant predictor of relapse was pretreatment PSA. There were no complications > Grade 3. CONCLUSIONS: In spite of the inability to achieve high tumor temperatures, the relapse-free survival rate in this population of patients with very advanced localized prostate cancer treated with radiation therapy plus hyperthermia compares favorably with most series using radiation therapy alone. Further studies aimed at improving the ability to deliver hyperthermia to the prostate are warranted.

Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck.

PURPOSE: Tumor hypoxia adversely affects short term clinical radiation response of head and neck cancer lymph node metastases and long term disease-free survival (DFS) in cervix carcinoma. This study was performed to evaluate the relationship between tumor hypoxia and DFS in patients with squamous carcinoma of the head and neck (SCCHN). METHODS AND MATERIALS: Pretreatment tumor pO2 was assessed polarographically in SCCHN patients. All patients were AJCC Stage IV and had pretreatment oxygen measurements taken from locally advanced primaries (T3 or T4) or neck nodes > or = 1.5 cm diameter. Treatment consisted of once daily (2 Gy/day to 66-70 Gy) or twice daily irradiation (1.25 Gy B.I.D. to 70-75 Gy) +/- planned neck dissection (for > or = N2A disease) according to institutional treatment protocols. RESULTS: Twenty-eight patients underwent tumor pO2 measurement. The average pre-treatment median pO2 was 11.2 mm Hg (range 0.4-60 mm Hg). The DFS at 12 months was 42%. The DFS was 78% for patients with median tumor pO2 > 10 mm Hg but only 22% for median pO2 < 10 mm Hg (p = 0.009). The average tumor median pO2 for relapsing patients was 4.1 mm Hg and 17.1 mm Hg in non-relapsing (NED) patients (p = 0.007). CONCLUSION: Tumor hypoxia adversely affected the prognosis of patients in this study. Understanding of the mechanistic relationship between hypoxia and treatment outcome will allow for the development of new and rational treatment programs in the future.