Clinical stage II non-small cell lung cancer treated with radiation therapy alone. The significance of clinically staged ipsilateral hilar adenopathy (N1 disease).

BACKGROUND: The prognosis of patients with clinically staged hilar nodal involvement (Stage N1) or clinical Stage II non-small cell lung cancer (NSCLC, Stage T1-2N1M0) treated with radiation therapy (RT) alone is not well established. METHODS: Records of 758 patients with clinical Stage I-III NSCLC treated with RT were reviewed. Sixty-two patients were identified with clinical Stage II NSCLC, and 126 patients had Stage N1 disease. RESULTS: The median survival time (MST) of the 62 patients with clinical Stage II disease was 17.9 months, with 1-year, 2-year, 3-year, and 5-year overall actuarial survival rates of 70%, 33%, 20%, and 12%, respectively. The survival of patients with clinical Stage II disease was significantly better than that of 389 patients with clinical Stage IIIA disease (MST, 11.3 months; P < 0.008) and 267 patients with clinical Stage IIIB disease (MST, 9.8 months; P = 0.0003), but it was similar to that of 40 patients with clinical Stage I lesions (MST, 15.0 months). Patients with performance statuses of 0-1 lived longer than those with a status of 2 or more (MST, 22.8 versus 6.1 months; P < 0.0001). The median survival for patients with N0, N1, N2, and N3 disease was 13.7, 12.6, 10.9, and 9.1 months, respectively. Patients with Stage N0-1 disease (MST, 13.2 months) had significantly improved MST compared with those with Stage N2-3 disease (MST, 10.3 months). CONCLUSIONS: The survival of patients with clinical Stage II NSCLC treated with RT alone was significantly better than that of those with clinical Stage IIIA or IIIB disease. It was comparable to that of patients with clinical Stage I lesions. The clinical staging of nodal involvement limited to the ipsilateral hilum does not necessarily portend a worse prognosis than that of patients with clinical Stage N0 disease. The absence of clinically evident Stage N2-3 disease is of significant predictive value for patients with NSCLC treated with RT.

Use of computerized hot wire block cutter in radiation therapy.

The ability to define the target volume more accurately and to deliver the radiation therapy with better precision in modern radiation oncology has resulted in radiation treatments with tighter margins in order to spare additional normal tissues. This type of treatment requires that the radiation shielding blocks be produced with high accuracy. The computer-driven block cutter has the advantage of being able to accept block contours designed from digital simulation and portal images as well as beam's-eye-view patterns produced during treatment planning. A computerized hot wire block cutter installed in our department has shown the capability to produce accurate blocks and has reduced the number of blocks requiring modifications by about one-third. The use of templates plotted on the transparencies facilitates the accurate mounting of the blocks has resulted in further reduction of the number of block modifications.

Endometrial cancer with para-aortic adenopathy: patterns of failure and opportunities for cure.

PURPOSE: To examine the outcome of patients with advanced endometrial cancer whose para-aortic involvement was diagnosed pathologically or lymphographically. METHODS AND MATERIALS: Fifty patients from four institutions were treated between 1959 and 1990 with preoperative, post-operative, and primary radiotherapy. Para-aortic disease was diagnosed pathologically in 26 patients and lymphographically in the remaining 24 patients. Pathologically diagnosed patients underwent debulking of grossly involved nodes. All patients received external beam treatment through pelvic and para-aortic portals. Median prescribed dose to the pelvic and para-aortic fields was 50 and 47 Gy, respectively. Those treated with primary or pre-operative irradiation also received intrauterine brachytherapy. RESULTS: The actuarial 5-year disease-free survival was 46% for all patients. Para-aortic failure was significantly decreased among patients undergoing lymph node resection (13% versus 39%, respectively). Relapse-free survival and pelvic control tended to improve among patients receiving surgery plus irradiation in comparison to those treated by irradiation alone. Distant metastases were most common among patients with high grade lesions. CONCLUSIONS: Long-term disease-free survival is achievable in endometrial cancer patients with para-aortic lymphadenopathy who are treated with extended-field radiotherapy. Cure is mot attainable among patients with well differentiated, early clinical stage disease who receive combined modality treatment. Survival and local failure are similar for radiologically and pathologically diagnosed patients; however, para-aortic failure as a component of local failure was increased in patients who did not undergo surgical debulking of the adenopathy.

Comparison of outcome between clinically staged, unresected superior sulcus tumors and other stage III non-small cell lung carcinomas treated with radiation therapy alone.

Several studies suggest that patients with non-small cell lung carcinoma (NSCLC) of the superior sulcus fare better after radiation therapy than those patients with comparable tumors at other thoracic sites. There is limited data on stage-by-stage comparisons between patients with superior sulcus tumors (SST) and non-SST (NSST). Thirty patients had SST among 656 patients with American Joint Committee on Cancer clinically staged IIIA (n = 389) and IIB (n = 267) primary NSCLC who received definitive once-daily radiation therapy. The median patient age, sex ratio, histologic findings, grade, weight loss, and performance status were similar for SST and NSST. Minimum follow-up was 24 months, with 88% of patients followed until death. The survival of patients with SST (median, 10.3 months) was similar to that of patients with tumors at other pulmonary sites (median, 10.8 months; P = 0.39). Survival for favorable patients with performance status 0 to 1 and weight loss of 5% or less was comparable between patients with SST (median, 15.0 months) and NSST were similar for patients with SST and NSST (P = 0.48). The brain was the site of first failure in 20% of patients with SST and 10% of patients with NSCLC at other sites (P = 0.10). The lack of apparent difference in outcome of comparably staged patients with SST and NSST treated with radiation alone may have significant therapeutic implications.

Should patients with post-resection locoregional recurrence of lung cancer receive aggressive therapy?

The outcome of thirty-seven patients with a post-resection locoregional recurrence of non-small cell lung cancer treated with radiation therapy alone between 1979 and 1989 was compared to that of 759 patients with unresected non-small cell lung cancer also treated with standard radiation during the same period. Each patient's locoregional recurrence was staged using the current American Joint Committee on Cancer staging system. Comparison of pretreatment characteristics between the two groups, including age, sex, extent of weight loss, performance status, stage, and histologic subtype revealed fewer patients with greater than 5% weight loss (35 vs. 47%, p = 0.04) and more cases with squamous histology (54 vs. 28%, p = 0.01) among the patients with locoregional recurrences than those with newly diagnosed lesions. Over 80% of both groups had clinical stage III lesions. The median radiation doses were 56 and 59 Gy for recurrent and newly diagnosed cases (p = NS). For the patients with locoregional recurrences, the median time from resection to recurrence was 13 months (range: 3-118 months), and the recurrences were predominantly nodal in 25 cases, chest wall/pleural in four and at the bronchial stump in eight. When measured from the date of documented recurrence, the median survival time and 2-year actuarial survival rate of the patients with recurrent lesions were 12 months and 22%, as compared to 12 months and 26% for the newly diagnosed patients (p = NS). Freedom from documented locoregional tumor progression at 2 years was 30% for both groups. Patients with bronchial stump lesions had superior survival to those with nodal or chest wall recurrences, with a median survival time of 36 versus 9 months. A therapeutic approach to selected patients with post-resection locoregional recurrence of non-small cell lung cancer equally aggressive to that for newly diagnosed lung cancer patients is justified by these results, especially for patients with bronchial stump recurrences.

Adverse influence of younger age on outcome in patients with non-small cell lung carcinoma (NSCLC) treated with radiation therapy (RT) alone.

Treatment outcome of 63 patients younger than 50 years of age initiated on a course of once-daily definitive radiation therapy without concurrent or preirradiation chemotherapy for clinical Stages I-III unresected non-small cell lung carcinoma from 1978 to 1988 was compared to the outcome of 695 patients over the age of 50. Follow-up ranged from 24-110 months with follow-up until death in 88% of patients. The actuarial overall survival rate for all patients was 22% at 2 years with a median survival time of 11.5 months. Patients less than 50 and greater than or equal to 50 years old were similar in male:female ratio, distribution of histologic subtype, performance status, and extent of weight loss. Poorly differentiated histologic grade was more prevalent among the younger patients (59% vs 41%, p = .005). Ninety-four percent of younger patients and 86% of older patients had clinical stage III disease (p = NS). Survival was significantly worse for patients who were younger than 50 years old (p = .05), with a median survival time of 7.8 months. Median survival time for those patients 50 years of age or older was 12.4 months. Poorer survival outcome among young patients was most pronounced among patients with unfavorable characteristics of poor performance status (greater than or equal to 2) or weight loss (greater than 5%) (p = .002). Distant failure (p = .029) and brain failure (p = .003) as initial site of relapse was more common among younger patients. Among young patients, poor histologic grade was associated with both distant failure (p = .003) and brain metastasis (p = .002). The difference in distribution of histologic grade, incidence of distant failure, particularly in the brain, and poorer survival outcome among patients less than 50 may be indicative of more aggressive tumor behavior in the younger patients. These results indicate that patients less than 50 may require alternate treatment strategies. Age should be considered a stratification variable in non-operative randomized trials of non-small cell lung carcinoma which include patients with non-favorable characteristics.

Significance of prone positioning in planning treatment for esophageal cancer.

The treatment of esophageal cancer is made difficult by the close proximity of the esophagus to the spinal cord and the requirement to treat the esophageal target volume to doses greater than or equal to 60 Gy while limiting the spinal cord dose to less than or equal to 46 Gy. By placing the patient in the prone position, the esophagus can be displaced away from the spinal cord. We explored the results of this commonly used technique on 16 patients who have undergone simulation in both supine and prone positions. Both AP and lateral orthogonal radiographs were obtained in both positions. The distance between contrast material in the esophagus and spinal cord was noted in at least four transverse planes through the thoracic esophagus on each of the 16 patients. These four transverse planes were located at 3 cm above the carina, at the carina, 3 cm below the carina and 6 cm below the carina. The mean displacement (+/- 1 SD) of the esophagus away from the spinal cord when the patient was in the prone position compared to supine at each of these levels was 1.3 (+/- 0.8) cm, 1.8 (+/- 0.9) cm, 1.8 (+/- 1.0) cm, and 1.9 (+/- 1.1) cm. The range of displacement for all 64 displacement determinations was 0 to 4.2 cm with a mean of 1.7 cm. To evaluate further the consequences of prone positioning on treatment planning and doses received to target volumes and critical structures, we performed 3-dimensional treatment planning with a patient in both prone and supine positions. The requirements were to achieve a tumor volume dose of 60 Gy while keeping the spinal cord dose below 46 Gy. Two types of conventional treatment plans were examined in prone and supine positions. A 6-field plan consisted of delivery of 40 Gy through a large 3-field beam arrangement followed by delivery of 20 Gy through a similar 3-field cone down. An 8-field plan involved the delivery of 30 Gy through AP/PA beams followed by a 3-field beam arrangement to 40 Gy and a subsequent 3-field cone-down for the final 20 Gy. Comparison of dose volume histograms revealed that the 6-field plan spared relatively more heart whereas the 8-field plan spared relatively more lung. Regarding the primary consideration of coverage of target volume with avoidance of spinal cord, prone positioning was superior to supine positioning whether 6- or 8-field arrangements were used.

Dose to superficial node for patients with head and neck cancer treated with 6 MV and 60Co photons.

The superficial neck nodes in only 1 out of 7 patients with head and neck cancer studied received more than 90% of the prescribed dose when treated with opposed 6 MV photons. Beam spoilers placed upstream from the patient enhanced the dose to the superficial node at the expense of higher dose to the skin.

Digital imaging in the radiation oncology environment: a personal computer local area network solution.

Personal computer (PC) driven digital imaging devices are now becoming available in the market place for use in radiation oncology to produce what are known as real time portal images. These limited contrast images are used to verify the patient anatomy under treatment by megavoltage x-rays and are a vital part of the patient treatment. The current generation of devices can produce both single and movie loop images in real time for physician review and approval. To disseminate these images and other digital images used in the planning and delivery of radiation therapy, a PC-based picture archiving and communications system has been developed that is tailored to the special needs of radiation oncology.

Decreasing gastrointestinal morbidity with the use of small bowel contrast during treatment planning for pelvic irradiation.

Small bowel tolerance is a major dose-limiting factor in treating the pelvis with radiation therapy (RT). The use of small bowel contrast during RT simulation is one technique used to localize the bowel and identify the treatment plan that would exclude the greatest volume. To determine the influence of treatment planning with oral contrast on gastrointestinal injury, acute and chronic small bowel morbidity was analyzed in 115 patients with endometrial and rectal carcinoma who received postoperative radiation therapy at the Fox Chase Cancer Center. Mean and median time of follow-up were 31 and 27 months, respectively. Acute diarrhea was seen in 82% of the patient population. Ten percent of patients experienced major complications requiring hospitalization. Ninety-three percent of patients simulated without contrast experienced side effects compared to 77% of patients simulated with contrast (p = .026). There was an increased incidence of chronic complications in patients who were not simulated with contrast dye (50% vs 23%, p = .014). Median duration of minor side effects was 4 months for patients planned without oral contrast and 1 month for patients who had contrast at the time of simulation (p = .036). The superior aspect of the treatment field was determined to be at a more inferior location in patients simulated with contrast, thereby excluding small bowel from treatment. Seventy-four percent of patients simulated without contrast had the upper border of the field placed at the superior aspect of the sacroiliac joint or above, compared to only 40% of patients planned with oral contrast (p = .002). This study has demonstrated decreased complications (both overall and chronic) as well as a change in the location of the treatment field with the use of small bowel contrast. Multivariate analysis revealed that both the use of oral contrast (p = .026) and a lower superior border of the treatment field (p = .007) were predictive for fewer sequelae to RT, indicating that planning with contrast leads to changes in the technical delivery of RT other than field placement (e.g., block placement). The reduced incidence and duration of small bowel morbidity may be in part caused by alterations of the treatment plan made when the small bowel is visualized at the time of simulation. It is therefore recommended that oral small bowel contrast be used during treatment planning for pelvic irradiation.

Long-term results of infusional 5-FU, mitomycin-C and radiation as primary management of esophageal carcinoma.

An analysis of the results of 90 patients with esophageal cancer treated prospectively with combined chemotherapy and radiation without surgery and with a median follow-up of 45 months is presented. Fifty-seven patients with Stage I or II disease received definitive treatment consisting of 6,000 cGy in 6 to 7 weeks and 5-FU (1,000 mg/m2/24 hr) as a continuous intravenous (IV) infusion for 96 hours, starting on days 2 and 29. Mitomycin C (10 mg/m2) was administered as a bolus injection on day 2. Thirty-three patients received palliative treatment (5,000 cGy plus above chemotherapy) for Stage III, IV, or otherwise advanced disease (extraesophageal spread, distant metastases, multiple primary tumors). Follow-up ranged from 1 month to 96 months. Overall median survival of Stage I and II patients was 18 months with 3- and 5-year actuarial survival of 29% and 18%, respectively, while the median disease specific survival was 20 months with an actuarial disease specific survival of 41% and 30% at 3 and 5 years, respectively. A multivariate analysis of sex, histology, tumor location, and tumor size on survival revealed that the effect of stage was highly significant (Stage I versus II, 73% versus 33% at 3 years, p = .01), whereas the effect of sex approached significance (females versus males, 57% versus 34% at 3 years, p = less than .1). The actuarially determined local relapse-free rate for Stage I and II patients at both 3 and 5 years was 70%. Multivariate analysis again indicated stage to be highly significant (Stage I versus II, 100% versus 60% at 3 years, p = less than .01), whereas sex approached significance (female versus male, 75% versus 66% at 3 years, p = .07). The pattern of failure may be altered with this treatment regimen from local to one dominated by distant metastases. Of 29 patients who have failed, 14 (48%) had any component of local failure, whereas 21 (72%) had a distant failure as a component of failure. The median survival of patients with Stage III or IV disease was 9 months and 7 months, respectively. Palliation in this group of patients with advanced disease was good as 77% were rendered free of dysphagia post-treatment, and 60% were without dysphagia until death with a median dysphagia-free duration of 5 months. Severe toxicities were uncommon and nearly all were transient. Eleven of 90 patients (12.2%) had severe acute toxicities, whereas only 3 patients (3.3%) developed significant late treatment-related complications requiring hospitalization for management.

Lack of apparent difference in outcome between clinically staged IIIA and IIIB non-small-cell lung cancer treated with radiation therapy.

The current American Joint Committee on Cancer (AJCC) staging system for bronchogenic carcinoma, which divides stage III M0 cases into stages IIIA and IIIB, is based on the observation that selected patients with IIIA disease (T3 or N2) can undergo complete surgical resection, in distinction to IIIB patients (T4 or N3). To understand the value of this system when applied to clinically staged (CS) patients treated with a standard nonoperative approach, the records of patients with squamous cell, large-cell, and adenocarcinoma of the lung treated with radiation therapy (RT) at the Fox Chase Cancer Center from 1978 to 1987 were reviewed. Three hundred sixteen patients were identified as having CS III M0 disease treated with single daily fraction RT without chemotherapy or sensitizers. Of these, the distinction between IIIA (166) and IIIB (140) could be made for 306 patients. The median survival time (MST) for all CS III patients was 9.6 months, and the 2-year survival was 17%. No difference was observed in MST between CS IIIA and IIIB patients (9.4 v 9.8 months, P = .78), in 2-year survival (17% v 18%), or in rate of first failure within the RT field (43% v 44%). MSTs for the 157 CS IIIA and IIIB patients with less than 5% weight loss and Zubrod performance status (PS) 0 to 1 were 13.0 and 15.8 months (P = .29), respectively. This lack of difference in outcome for CS IIIA and IIIB patients receiving RT has important implications in the design and stratification of future nonoperative trials for stage III lung cancer.

Equipment and manpower needs in radiation oncology dosimetry and treatment delivery.

Information on the patterns of personnel and equipment support at various radiation oncology facilities are included in the Facilities Master List surveys conducted by the American College of Radiology. This paper summarizes the surveyed data on equipment and dosimetrist and technologist support obtained during 1975-1986. There is increasing use of linear accelerators, simulators, and treatment planning computers but the use of 60Co units has been progressively decreasing. There are inadequate but slowly improving numbers of dosimetrists and technologists when compared with the level recommended by the Blue Book.

Patterns of change in the physics and technical support of radiation therapy in the USA 1975-1986.

Information on the patterns of personnel and related equipment support and availability at various types of radiation oncology facilities are included in the Facilities Master List surveys conducted by the American College of Radiology. This paper summarizes the surveyed data obtained during 1975-1986. The data presented include the use of equipment and the degree of personnel support at government owned, hospital or university based, and freestanding facilities. There is increasing use of linear accelerators, simulators, and treatment planning computers among all types of facilities. The use of 60Co units has been progressively decreasing. Almost all types of facilities show inadequate, but slowly improving, numbers of physicians, physicists, dosimetrists, and technologists when compared with the level recommended by the Blue Book.

Physical characteristics of the M.D. Anderson Hospital clinical neutron beam.

The physical characteristics of the M.D. Anderson Hospital (MDAH) clinical neutron beam are presented. The central-axis percent depth-dose values are intermediate between a 4 and 6 MV X-ray beam. The build-up curves reach a depth of maximum dose at 1.2 cm and have surface dose values of approximately 30%. Teflon flattening filters are employed to flatten the beam at the depth of the 75% dose level. Two wedges are available for shaping the beam; they are made of Teflon and produce wedge angles of 31 degrees and 45 degrees as defined by the ICRU. Output factors ranged from 0.88 for a 4 x 4 cm field to 1.12 for a 20 x 20 cm field. Tungsten blocks reduced the dose received at Dmax to 25% of the unblocked value but only 52% of the unblocked value at a depth of 22.8 cm.

Cell survival and recovery processes in Chinese hamster AA8 cells and in two radiosensitive clones.

Cell survival and recovery after gamma irradiation were investigated in a Chinese hamster ovary cell line (AA8) and in two radiosensitive clones (EM9 and NM2) derived from it. When analyzed by the multitarget and linear-quadratic equations, the dose-response curves for survival of both EM9 and NM2 cells, compared with AA8 cells, were characterized by a decreased magnitude of the shoulder or single-hit region (as reflected by Dq or alpha, respectively) but no difference in the terminal slope or double-hit region (as reflected by DO or beta, respectively). Recovery from sublethal damage (SLD) and potentially lethal damage (PLD) was measured in the three cell lines to examine the relationship between the shoulder width of the survival curve and the magnitude of cellular recovery. NM2 cells exhibited a reduced shoulder on their survival curve and a reduced capacity for SLD recovery, compared with AA8 cells, after equitoxic doses of radiation. EM9 cells, which also had a reduced shoulder on their survival curve, displayed the same rate and extent of recovery as AA8 cells for both SLD and PLD. PLD recovery, as assayed in fed plateau-phase NM2 cells by delayed plating, occurred with slower initial kinetics but to the same final extent as that in AA8 cells, resulting in modification of both the shoulder and the slope of the survival curve. However, PLD recovery, as assayed in log-phase NM2 cells by postirradiation treatment with hypertonic salt, was normal and affected predominantly the slope of the survival curve. These data demonstrate that although both SLD and PLD recovery play a role in determining cell survival, cell-survival curve parameters may not always be useful in predicting cellular recovery capacity.

Measurement of the dose equivalent of leakage radiation through an isocentric gantry used for neutron therapy.

The leakage radiation through the shielding on an isocentric gantry of a neutron therapy machine was measured with a Rossi-type proportional counter. The dose equivalent of the leakage radiation was determined at two positions: (1) in the plane of the patient and (2) in the plane of the target. The dose equivalent of the leakage radiation is approximately the same as the leakage of a high-energy x-ray linac.

A microdosimetric characterization of a cyclotron-produced therapeutic neutron beam.

The therapeutic neutron beam of the Cyclotron Corporation's CP-42 negative-ion cyclotron is generated by protons of 42 MeV bombarding a thin beryllium target. Microdosimetric measurements were made for this neutron beam in a full-scatter water phantom at nine positions inside and outside the useful beam. The lineal energy distribution and the variations of dose-mean, frequency-mean, and saturated lineal energy are compared for these positions. The dose fraction due to gamma rays is also calculated at each of these positions, based upon previously published techniques. A theoretical relative biologic effectiveness, based upon the dual radiation action model of Kellerer and Rossi [Curr. Top. Radiat. Res. 8, 85 (1972)] is also shown for the positions of measurement.