Fractionated half-body irradiation (HBI) for the rapid palliation of widespread, symptomatic, metastatic bone disease: a randomized Phase III trial of the International Atomic Energy Agency (IAEA).

PURPOSE: To find the fastest and most effective/efficient method to economically deliver fractionated half-body irradiation (HBI) for widespread (WS), symptomatic, metastatic bone cancer. METHODS AND MATERIALS: A Phase III trial with 3 HBI arms: (Arm A) Control (15 Gy/5 fractions/5 days); (Arm B) Hyperfractionation (HF) (8 Gy/2 fractions/1 day); (Arm C) Accelerated HF (12 Gy/4 fractions/2 days). Six countries randomized 156 patients (all with WS bone metastases): 51, 56, and 49 patients to Arms A, B, and C, respectively. There were 72 (46%) breast, 50 (32%) prostate, 9 (6%) lung, and 25 (16%) miscellaneous primary tumors. Initial performance status (PS) was 1-2 in 101 (65%) and PS 3-4 in 55 (35%). The lower, upper, and middle halves of the body were treated 79, 68, and 9 times. RESULTS: Pain relief was seen in 91% of patients (45% complete [CR] and 46% partial [PR]) within 3-8 days. Overall (OS), median (MST), and pain-free (PFS) survival was 174, 150, and 122 days. Breast tumors had a higher OS (279 days) than that of other primary tumors, but when analyzed by treatment, was not significantly different than prostate tumors in Arm A. No survival differences were found in patients with PS 1-2 vs. 3-4, CR vs. PR, bone with/without visceral metastases, or by the number of metastases (< or > 15 bone lesions). Quality of life (QOL) assessed by the percent of the remaining life free of pain was 71%; furthermore significant improvements in PS, pain, and narcotic scores were seen after HBI. Toxicity was very acceptable (41% none, 50% mild/moderate, 12% severe but transitory); more was seen with upper HBI. CONCLUSION: In terms of response, time to response, OS, MST, PFS, QOL, and toxicity, schedules for Arms A and C were similar for all but prostate primaries. Schedule for Arm B, which delivered the lowest biologic dose in the shortest time, had significantly worse results in pain relief, OS, MST, PFS, and QOL. Results indicate that, for most primary tumor types (except prostate), delivering two HBI daily doses of 3 Gy in 2 consecutive days is as effective as delivering a daily dose of 3 Gy for 5 consecutive days. Thus, this is a faster and much more convenient HBI schedule for the palliation of pain in widespread cancer.

Theoretical and practical uses of elective systemic (half-body) irradiation after 20 years of experimental designs.

This article traces the concept and different uses of systemic (Half-Body) irradiation (HBI) for the last 20 years. It presents both indirect and direct evidence of HBI effectiveness and discusses the various hypothesis that have been advanced to explain its success as a palliative and more recently as an elective therapeutic tool. The article discusses the transition from treating overt to subclinical metastatic disease and recalls the pioneer uses of elective HBI in lung and prostate cancers. Recent uses of elective HBI with a variety of unconventional fractionation schemes are discussed. These include clinical trials (51 patients with lung, esophagus, colorectal, prostate, ovary and endometrial cancers) and animal experiments (1195 C3H mice). An intriguing combination of hyper/hypo fractionated HBI proved to be the less toxic of all the schedules used in animals where mortality data, analyzed by the LQ Model, yielded an alpha/beta ratio of 8.3 Gy, a value generally associated with acutely responding tissue.

Fractionated half-body irradiation for pain palliation in widely metastatic cancers: comparison with single dose.

PURPOSE: To explore fractionated half-body irradiation (HBI) for pain palliation and determine if it is more efficient and effective than single dose HBI. METHODS AND MATERIALS: During the last 13 years, 75 out of 115 HBIs (64%) at the University of Maryland Medical Center were given for palliation of various widely metastatic cancers (28% prostate, 25% breast, 12% lung). The HBI fields were 28% upper, 25% mid, and 47% lower; three patients had both upper and lower HBI. An initial performance status (PS) 3&4 with a life expectancy < 3 months was found in 50% of patients. The HBI techniques used on consecutive patients were: single dose (SD) in 54% with escalating doses of 4-10 Gy; split-course (SC) in 12% with two 4 Gy single doses separated by 2 weeks; and daily fractionated (DF) in 34% with five fractions of 3 Gy each. There were 68 of 75 HBI (91%) given for pain control purposes. RESULTS: The percent total (complete) pain relief was SD-73(32), SC-50(13), and DF-96(49). Time to maximum and (complete) relief was: SD 5 days each and DF HBI 7(11) days. Pain-free survival (PFS) was short but so was overall survival (OS). PFS was SD-5, SC-4.5, and DF-19 weeks. The percent of the remaining patient's life spent pain free without retreatment (NPR) was SD-38, SC-34, and DF-68. Differences in pain relief, PFS, OS, and NPR were significant and carried over primary tumor types; prostate, breast, and surprisingly GI were very responsive (90, 84, and 83%, respectively). On multivariate analysis only the PS and degree of relief were independent variables. Despite lack of premedication in DF-HBI, toxic reactions were identical to SD-HBI with premedication. No Grade 4 toxicities occurred. Grade 3 toxicities were 4%. Retreatment was 3% in SD and 13% in fractionated HBI; these differences were not significant. CONCLUSION: HBI is still the most effective and efficient way to palliate pain from widely disseminated cancer. Fractionating HBI eliminates need for the premedication and close patient monitoring required for SD-HBI. It also allows for an increase in total dose which can produce better responses in pain relief, duration of relief, PFS, OS, and quality of life.

Role of radiation therapy in the management of malignant chondroid syringoma.

BACKGROUND: Malignant sweat gland neoplasms are exceedingly rare tumors. Malignant chondroid syringoma (MCS) is one of the rarest subtypes, and as such, still poorly understood. It lacks distinctive clinical features, often delaying initial diagnosis and therapeutic management. OBJECTIVE: A current case and the available literature are reviewed to determine the overall clinical course of the MCS and the potential role of adjuvant therapy. METHODS: A case of MCS was studied by light microscope, immunohistochemistry, and electron microscopy. The clinical data of this case and of other reported cases are summarized and compared. RESULTS: This tumor recurred locally after initial local excision. Subsequent re-excision and radiation therapy rendered the patient without evidence of disease. This case study and the literature review of the 20 reported cases indicate that MCS is highly recurrent with tendency toward metastasis. CONCLUSION: MCS appears to behave in an aggressive manner. An initial treatment modality is aggressive surgery. Adjuvant radiation therapy with or without chemotherapy should be tried in future cases.

Combined carboplatin plus bleomycin and conventional radiotherapy for advanced carcinomas of the head and neck.

In a previous study, we reported a 72% response rate (CR = 52%) in patients with unresectable head and neck (H&N) carcinomas treated with simultaneous carboplatin (CBDCA) and radiotherapy (RT). Bleomycin (Bleo), a known radiosensitizing agent, has been shown to increase response rates when given together with RT in similar patients. To explore the nonoverlapping toxicities of these two agents, we combined i.v. CBDCA (100 mg/m2/week), Bleo (5 units on day 1 and 4/weekly) and standard doses of RT in patients with unresectable H&N carcinomas. Chemotherapy (CT) was continued until completion of RT. Twenty-three (13 males, 10 females) previously untreated patients with stage IV squamous cell carcinoma of the H&N were treated at the University of Maryland Medical Center: 61% had oropharyngeal cancers; 26%, hypopharynx; 9%, oral cavity; and 4%, an unknown primary. Moderate to severe mucositis developed in 90%, which required RT interruptions of up to 3 weeks. After a median follow-up (FU) of 18 months, 35% achieved a complete response (CR) and 65% died from progressive disease. These preliminary data suggest that the addition of Bleo increases mucosal toxicity substantially and, while a moderate response rate was observed, it is unlikely that the CR rate will be higher than CBDCA/RT, which was also better tolerated and hence more suitable to multimodal approaches.

Pelvic mass: CT-guided interstitial catheter implantation with high-dose-rate remote afterloader.

A technique is presented for computed tomography (CT)-guided interstitial catheter placement and treatment planning for high-dose-rate brachytherapy. In a 66-year-old woman with adenocarcinoma of unknown origin that had metastasized to the right ilium, interstitial brachytherapy catheters were placed by means of CT guidance. With use of a treatment planning system with dose optimization, an excellent dose distribution was obtained with minimal dose being delivered to the surrounding critical tissues. For selected patients, this procedure can provide effective and safe local treatment for solid tumors.

Colorectal cancer: metastatic patterns and prognosis.

From 1979 to 1982, 163 patients with colorectal cancer were found to have distant metastases. Of these, 112 (69%) had metastatic disease at the time of initial diagnosis (synchronous metastases [SM]); in the remaining 51 (31%) metastases developed during the course of the disease (metachronous metastases [MM]). The liver was the most common site of metastasis in both groups (72% and 65%, respectively); with the exception of brain metastasis, liver metastasis had the worst prognosis (median survival time [MST], 9 months). The MST for other sites of metastasis were: lung, 10.5 months; bone, 10 months; multiple sites, 10 months; and brain, 5.5 months. Of the 81 patients with SM in the liver, 38% were treated with single modality therapy and 62% with combined modality therapy. Thirty-three patients had MM in the liver. The median time for development of liver metastases (metastasis-free interval [MFI]) was 17.5 months; only lung metastases developed faster (12 months). MFIs for other sites were 20, 20.5, and 33 months for bone, multiple sites, and brain, respectively.

Radiation therapy for chest recurrences following induction chemotherapy in small cell lung cancer.

Once small cell lung cancer fails induction chemotherapy, second line drugs are usually ineffective, accounting for mostly partial responses in the order of 0-20% and a median survival of 6-10 weeks. A review of patients with relapsed small cell lung cancer was carried out at the University of Maryland. Of 51 such patients, 44 received thoracic irradiation at the time of relapse. Excluding 8 patients who received insufficient treatment, the series consists of 36 patients (27 with limited and 9 with extensive disease) and represents the largest experience with relapsed small cell lung cancer subjected to radiation alone. Total radiation doses were 60 Gy in 11, 45-55 Gy in 14, and 38-42 Gy in the remaining 11 patients. No second line chemotherapy was given simultaneously with radiation at time of relapse and it was only given subsequently during the course of the disease to four patients. Responses to radiation were seen in 28 (77%) with 9 (25%) complete and 19 (52%) partial. The median survival was 16-40 weeks varying with disease extent, response, and total dose. Subsequent failures occurred in chest (34%) and distant sites (66%). A dose-response curve was attempted; the higher doses achieved as much as 75% local control. A poor response to induction chemotherapy did not predict a poor radiation response at time of relapse. Nearly 2/3 of patients who had not responded to induction chemotherapy responded to radiation at the time of relapse. The post-recurrence survival after radiation therapy was as long as or longer than the recurrence-free interval after induction chemotherapy, and this clearly demonstrates the value of radiation in achieving excellent palliation and good quality of life in these patients. Thoracic irradiation is recommended as a therapeutic alternative for locally recurrent small cell lung cancer after induction chemotherapy.

A differential low pH effect on tumour cells grown in vivo and in vitro when treated with hyperthermia.

The effectiveness of low extracellular pH in sensitizing cells to heat was studied using SCK mammary carcinoma cells of A/J mice. Solid tumours of 400-600 mg or cells grown in vitro for less than 13 weeks were dispersed to single cells and the in vivo- or in vitro-derived cells were suspended in a medium of pH 7.2 or 5.5-6.6 and then heated at 41-44 degrees C in vitro using a water bath. The dispersion procedure did not alter the heat sensitivity of these cells, but acidic medium of pH below 6.6 caused an increase in heat sensitivity. This effect of low pH decreased with increasing temperature of heating for both cell types. However, the effect was much smaller on in vivo-derived cells than that on in vitro-derived cells for any heating temperature tested. This reduction of the pH effect was also observed for cells derived from larger tumours as well as tumours at an early stage of growth in which the internal milieu was not acidic. This indicates that cellular adaptation to low intratumour pH was not the cause of the reduced pH effect; instead, factors other than low pH must cause the reduced pH effect seen in tumour-derived cells.

Heat-sensitive state of mouse mammary carcinoma cells in tumors.

The heat response of the SCK mammary carcinoma of A/J mice was studied in vivo and in vitro. Solid tumors or tumor cells in culture were heated in a water bath and cell survival was determined by clonogenicity in vitro. Cells in tumors were much more sensitive to heat than cells in culture. To eliminate vascular effects, tumors were dissociated into small fragments and the tumor fragments were heated in vitro, so that cells were heated while in contact with neighbors and in a complete medium. Cells in tumor fragments were as sensitive to heat as cells in tumors, even though vascular effects during heat exposure were excluded. The heat-sensitive tumor fragments gradually became heat resistant during 3 h of incubation in a complete medium at physiological temperature. The transition from a heat-sensitive to a heat-resistant state was not correlated with the development of thermotolerance or stress-related proteins. The transition was inhibited when the extracellular environment was made acidic or hypoxic but not when it was glucose and serum deprived. These results suggest that SCK tumor cells in vivo are sensitive to heat, and the heat-sensitive state appears to be established under the influence of the intratumor environment.

The role of post-operative radiation in the prevention of heterotopic ossification in patients with post-traumatic acetabular fracture.

Heterotopic ossification (HO) with subsequent pain and limitation of motion of the lower extremity is a common and significant problem for patients who suffer traumatic acetabular fracture (TAF). The incidence of heterotopic ossification is markedly increased for patients requiring surgical repair depending on the degree of trauma and the type of surgical repair necessary. Radiation therapy (RT) has proven to be the most effective surgical adjunct for the prevention of heterotopic ossification in patients undergoing total hip replacement (THR), but has not been reported in patients with traumatic fracture and repair. This report details an experience with patients treated at a Shock Trauma Center with extensile repair and immediate (within 48 hr) post-operative radiation therapy given as 5 daily fractions of 2 Gy in 5 to 7 days to a total dose of 10 Gy using megavoltage radiation therapy. A total of 30 consecutive patients (RT group) have been treated at our institution since June 1985. The last 20 patients treated with surgery only (non-RT group) prior to initiation of this study were used as a control group. Heterotopic ossification was seen to some degree in 50% of all radiation therapy patients, but was severe in only three of 30 (10%) of cases [three (10%) had Brooker III HO and no patients had ankylosis (Brooker IV HO)]. In contrast, some degree of heterotopic ossification was seen in 90% of the non-radiation therapy patients, and was severe in 10 of 20 (50%) of patients [seven (35%) had Brooker III HO whereas three (15%) had ankylosis (Brooker IV)]. This difference is significant for both total incidence and incidence of severe cases (p less than 0.01). This reduction in heterotopic ossification incidence approaches the magnitude reported for high-risk patients with total hip replacement. Even though the incidence of severe heterotopic ossification after radiation therapy for total hip replacement is approximately 5% and for traumatic acetabular fracture patients it is double (10%), the actual incidence of heterotopic ossification without radiation therapy is different in the two conditions. For total hip replacement, the incidence is about 30% and for traumatic acetabular fracture it is 50%. Radiation therapy has again proven itself to be an excellent surgical adjunct to prevent heterotopic ossification, this time in traumatic acetabular fracture patients.

Carboplatin (CBDCA) and radiotherapy for stage IV carcinoma of the head and neck: a phase I-II study.

The prognosis of patients with squamous cell carcinoma (SQC) of the head and neck (H&N) depends on the primary site and anatomical extent of the disease. Recurrence rates after conventional surgery (S) and/or radiotherapy (RT) remain low for localized tumors, whereas in advanced loco-regional disease they occur in over 60% of all cases. Several combinations of treatment modalities have been attempted in order to improve local control in Stages III and IV. Unfortunately, the recurrence rate remains high with added morbidity when conventional surgery is combined with pre or post-operative radiotherapy. Induction chemotherapy (CT) with Cisplatinum and Bleomycin has resulted in severe toxicities when combined with radiotherapy. To evaluate the toxicity of Carboplatin (CBDCA), a second generation platinum analog, when given simultaneously with conventional doses of radiotherapy, 26 patients with Stage IV SQC of the head and neck were treated at the University of Maryland Medical Systems. There were 23 males and 3 females; median age was 59 years and median Karnofski performance status was 60. Twenty patients had received no prior therapy; six had surgical exploration and excision with measurable residual disease. Anatomically, six patients had tumors of the oral cavity, twelve in the pharynx, one in the nasopharynx, four in the larynx, one in the hypopharynx, one in the maxillary antrum, and one was an unknown primary. These patients were treated as out-patients with weekly injections of Carboplatin. The dose was escalated: two patients received 60 mg/M2, seven received 75 mg/M2, thirteen were treated with 100 mg/M2, and four with 400 mg/M2. The radiotherapy was given daily with conventional fractions of 180 cGy and total tumor doses of 60-75 Gy. Toxicities were mainly hematological with median nadirs decreasing with increasing doses of Carboplatin. Mucositis was seen in over 80% of the patients, but interestingly enough, it has never been more severe than that observed with radiotherapy alone. So far, there has not been any kidney, ear, or neurotoxicities. Of 25 evaluable patients, 19 (76%) responded with 13 (52%) showing complete response. The overall median survival time is 266+ days (324+ for responders and 179+ for non-responders). The follow-up is still short, 10-14 months, but 9 of 13 patients with complete response have not yet progressed.

Breast cancer: metastatic patterns and their prognosis.

From 1969 to 1977, metastatic disease developed in 145 of the 558 patients treated for breast cancer at the University of Maryland Medical System. The most common first site of distant spread was bone (51%), followed by lung (17%), brain (16%), and liver (6%). The remaining 10% of patients had multiple metastatic sites. Fewer than 10% of the entire group received adjuvant chemotherapy after primary treatment. When metastatic disease appeared, most patients had palliative systemic chemotherapy and/or irradiation. In general, patients with initially negative axillary nodes had a longer median time until relapse (development of metastatic disease) and a longer survival time after diagnosis of metastases than patients with initially positive nodes. Liver was the least common initial metastatic site; while liver metastasis was seen only in patients with positive axillary nodes, it carried the worst prognosis. The overall median survival time after metastasis was 12 months for bone and lung lesions, three months for brain lesions, and only one month for liver metastasis. The median survival of patients with multiple metastatic sites was 7.5 months. No correlation was found between time until relapse and survival after metastasis. Patients in whom distant metastases developed relatively soon after the initial diagnosis had the same postmetastatic prognosis as patients whose disease metastasized later. No correlation was found between age at initial diagnosis and metastasis-free interval or survival after metastasis.

Once-a-week vs conventional daily radiation treatment for lung cancer: final report.

This is the final report of a prospective randomized clinical trial which began in 1982 and explored once-a-week hypofractionation in lung cancer patients with unresectable, non-metastatic, measurable, loco-regionally advanced disease. Stratification to this protocol has been done by histology, stage, and performance status categories. Patients with ipsilateral supraclavicular and/or brain metastases as the only evidence of distant spread, have been included in the study, but were stratified and analyzed separately. The two protocol arms were: (I) Conventional daily radiation [5 x W]-5 daily fractions of 2 Gy each to a total dose of 60 Gy in 6 weeks, protecting the spinal (SC) at 45 Gy and (II) Once-a-week radiation [1 x W]-one weekly fraction of 5 Gy each to a total tumor dose of 60 Gy in 12 weeks protecting the SC at 30 Gy. A total of 150 patients have been entered. Of these, 30 pts. are inevaluable, but the reasons of non-compliance, progression of disease or death due to intercurrent disease were of equal incidence in both groups. Of the 120 evaluable patients, 63 were treated 5 x W and 57 with 1 x W therapy. Complete tumor responses are similar in both arms with 1 x W pts demonstrating a numerical advantage (26% vs 17%). The average follow-up of the entire series is 3 yrs with a range of 12-66 months. Survival data is comparable in both groups with the 12 and 24 month actuarial survival of 49% and 23% for the 5 x W arm and 59% and 29% for the 1 x W arm. 1 x W patients continue to show a better tolerance than 5 x W pts. There are sufficient long-term survivors in both arms to assess chronic toxicity. The number of patients alive at 12, 18, and 24 months were 25, 11, and 5 for the 5 x W arm and 29, 16, and 7 for the 1 x W arm. No significant differences in late reactions have been noted. The longest surviving patient in the 1 x W arm is now 48 months after treatment.

A phase I/II trial of whole-abdominal plus pelvic irradiation for Astler-Coller stage beta 2, C colorectal cancer.

From 1982 to 1986, after radical surgery (S) for carcinoma of the rectum and rectosigmoid colon, 25 consecutive patients were entered into a Phase I/II study exploring adjuvant radiation (RT). The latter was given with a single fraction of whole abdomen (mid-body) irradiation (MBI), followed by conventional whole pelvis irradiation (WPI). The minimum follow-up time was 12 months, and the maximum was 44 months. There was escalation of the single MBI dose: 5 Gy in 11 patients, 6 Gy in two patients, and 8 Gy in 10 patients. The 2-year survival rate has been 100 and 45% for Stages B2 and C patients. Only 1/7 Astler-Coller Stage B2 patients failed; this failure was in the lungs. Seven of 15 patients with Stage C failed: one locally, three in the liver, and three in the lungs. Single MBI doses greater than 5 Gy have yielded a high incidence of intestinal obstruction when combined with routine WPI. Consequently, this combination requires both some modification and careful attention if used in future trials exploring new treatment approaches for colorectal cancer.

Radiation control in the intensive care unit for high intensity iridium-192 brain implants.

A bedside lead cubicle was designed to minimize the radiation exposure of intensive care unit staff during routine interstitial brain irradiation by removable, high intensity iridium-192. The cubicle shields the patient without restricting intensive care routines. The design specifications were confirmed by exposure measurements around the shield with an implanted anthropomorphic phantom simulating the patient situation. The cubicle reduces the exposure rate around an implant patient by as much as 90%, with the exposure level not exceeding 0.1 mR/hour/mg of radium-equivalent 192Ir. Evaluation of data accumulated for the past 3 years has shown that the exposure levels of individual attending nurses are 0.12 to 0.36 mR/mg of radium-equivalent 192Ir per 12-hour shift. The corresponding range for entire nursing teams varies between 0.18 and 0.26. A radiation control index (exposure per mg of radium-equivalent 192Ir per nurse-hour) is thus defined for individual nurses and nursing teams; this index is a significant guide to the planning of nurse rotations for brain implant patients with various 192Ir loads. The bedside shield reduces exposure from 192Ir implants by a factor of about 20, as expected, and the exposure from the lower energy radioisotope iodine-125 is barely detectable.

Single-dose half-body irradiation for palliation of multiple bone metastases from solid tumors. Final Radiation Therapy Oncology Group report.

This is the final analysis of Protocol #78-10 which explored increasing single-doses of half-body irradiation (HBI) in patients with multiple (symptomatic) osseous metastases. When given as palliation, HBI was found to relieve pain in 73% of the patients. In 20% of the patients the pain relief was complete; over two thirds of all patients achieved better than 50% pain relief. The HBI pain relief was dramatic with nearly 50% of all responding patients doing so within 48 hours and 80% within one week from HBI treatment. Furthermore, the pain relief was long-lasting and continued without need of retreatment for at least 50% of the remaining patient's life. These results compare favorably with those obtained by the Radiation Therapy Oncology Group (RTOG) using several conventional daily fractionated schemes on similar patients in a prior study (RTOG #74-02). HBI achieves pain relief sooner and with less evidence of pain recurrence in the irradiated area than conventionally treated patients. The most effective and safest of the HBI doses tested were 600 rad for the upper HBI and 800 rad for the lower or mid-HBI. Increasing doses beyond these levels did not increase pain relief, duration of relief, or achieved a faster response; however, the increase in dose was associated with a definite increase in toxicity. Single-dose HBI was well tolerated with no fatalities seen among 168 treated patients. A comprehensive premedication program has proven to decrease the acute radiation syndrome to very acceptable levels. There were excellent responses found in practically all tumors treated, but especially breast and prostate among which over 80% of all patients experienced pain relief, 30% in a complete fashion. Single-dose HBI emerges as one of the safest, fastest, and more effective palliative tools for intractable cancer pain in modern radiation oncology.

A prospective randomized trial comparing once-a-week vs daily radiation therapy for locally-advanced, non-metastatic, lung cancer: a preliminary report.

This is the first report of an on-going Phase III protocol for patients with locally-advanced, non-metastatic, measurable lung cancer. The study randomizes two arms: 6000 rad using 500 rad fractions once a week (1 X W) for 12 weeks with spinal cord (SC) protection at 3000 rad; and 6000 rad using 200 rad fractions daily (5 X W) for 6 weeks with SC protection at 4500 rad. Both arms use an initially large loco-regional field that is further reduced when tumor doses reach 3000 rad in (1 X W) arm and 5000 rad in (5 X W) arm. The protocol was activated April 1982; as of August 1984, it had accrued 100 patients of whom 68 were evaluable [29 (1 X W) and 39 (5 X W)]. There have been no major differences in tumor responses or failure patterns between the (1 X W) and (5 X W) arms; response rates have been 69 and 64%; CR 31 and 20%; total incidence of local failures 20 and 23%; and overall incidence of distant failures 34 and 43%, respectively. The (1 X W) arm has been far better tolerated with 76% of its patients free of any esophagitis and 97% without weight loss, as compared to only 33 and 67% in the (5 X W), respectively. The (1 X W) arm has not conveyed loss in tumor control effectiveness, in-treatment progression, or higher incidence of distant spread. Subacute and chronic complications have been minimal with either treatment. No fatal or life-threatening toxicities have occurred; the incidence of severe complications has been 7% in the (1 X W) arm and 8% in the (5 X W) arm. Nevertheless, the number of patients alive and at risk greater than or equal to 12 months is still relatively small; definitive statements regarding very late toxic reactions cannot yet be made. Compared to their protocyptes [a (1 X W) Pilot Study and the 6000 rad/6 weeks arm of RTOG Protocol 73-01], results in the present protocol arms have not been different from what was expected. Once a week RT yields results that appear no different from those achieved with conventional RT in lung cancer.