Combined modality treatment of extensive small cell lung cancer: a Southwest Oncology Group study.

The Southwest Oncology Group entered 453 patients with extensive small cell carcinoma into a combined modality treatment program, involving a randomized comparison of three different chemotherapy regimens for remission induction, and of maintenance chemotherapy alone versus maintenance treatment with cycles of reinduction added at six and 12 months. In addition, there was systematic comparison of diagnosis by institutional pathologist versus review panel pathologist. No difference was observed among the three different induction arms with respect to the incidence of response to treatment (61%), complete response (16%), or survival duration (median, 31 weeks). Neither overall response rate nor survival are superior to previous results. However, patients who achieved a complete response demonstrated significant survival benefit if they were in the group who received reinduction chemotherapy, as opposed to maintenance alone. This observation may apply most importantly to patients with small cell lung cancer of limited extent, for whom complete response is achieved in a majority. Agreement of institutional and review panel pathologists on the diagnosis of small cell lung cancer was observed in 94% of reviewed cases. A final observation is that the omission of chest irradiation results in a dramatic increase in the incidence of initial relapse at the primary tumor site. This suggests that future studies will need to use better therapy for local control in responding patients.

Multimodal therapy for limited small-cell lung cancer: a randomized study of induction combination chemotherapy with or without thoracic radiation in complete responders; and with wide-field versus reduced-field radiation in partial responders: a Southwest Oncology Group Study.

In 1979 we initiated a phase III study in the Southwest Oncology Group (SWOG) which was designed to determine the value of chest radiation in limited-stage small-cell lung cancer patients achieving complete response after induction chemotherapy, and to test the use of wide-field v more limited-volume radiation in patients with partial responses (PRs) and patients with stable disease (SD). The induction chemotherapy (VMV-VAC) consisted of vincristine, 2 mg intravenously (IV) every week for six doses; methotrexate, 60 mg/m2 IV days 1 and 43; VP-16, 50 mg/m2/d IV days 1 to 5 and 43 to 47; doxorubicin, 60 mg/m2 IV days 22 and 64; and cyclophosphamide, 1,000 mg/m2 IV days 22 and 64. Four hundred ninety-four patients were registered, of whom 473 were eligible. Of 466 response-evaluable patients, 153 (33%) achieved complete disease remission (CR) with chemotherapy. A total of 387 patients entered the consolidation phase of treatment after chemotherapy and response determination. CR patients were prospectively randomized to receive chest radiation, consisting of 4,800 rad administered in a split-course scheme, or to continue chemotherapy without interruption. The treatment volume was based on tumor extent before the induction chemotherapy. Maintenance chemotherapy consisted of cyclophosphamide and VP-16 administered for four cycles before a period of reinduction chemotherapy consisting of VMV-VAC as described above. Patients receiving chest radiation therapy were given the same maintenance and reinduction chemotherapy programs following completion of the chest radiation. One hundred ninety-one eligible patients achieving PR or SD status after induction chemotherapy were randomized to a preinduction treatment volume or to a postinduction reduced tumor volume, with treatment portals designed according to tumor extent before or after induction chemotherapy, respectively. After completion of the entire treatment plan, there were 218 (47%) CRs and 121 (26%) PRs. These figures represent the greatest response achieved at any point in the treatment program. The median survival for all eligible patients was 57 weeks (74 weeks for CRs). Overall survival for CR patients was not different for patients who did or did not receive chest radiation. However, patterns of tumor relapse were affected by the chest radiation, as 38 of 42 relapsing patients who did not receive radiation had intrathoracic recurrences in comparison to only 20 of 36 radiated patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Simultaneous chemotherapy-radiotherapy with prophylactic cranial irradiation for inoperable adeno and large cell lung carcinoma: a Southwest Oncology Group Study.

From September 1980 to March 1983, 30 cases were registered in a Southwest Oncology Group Study. Twenty-four cases were evaluable and constitute the basis for this report. Patients were diagnosed with adenocarcinoma or large cell lung carcinoma. Tumors were considered inoperable but able to be encompassed in a single radiotherapy (RT) port. Seventy-two percent of measured tumors were 4 cm in diameter or bigger (range 2 cm to 10 cm). RT was given initially to the primary lung tumor and ipsilateral hilar, mediastinal, and supraclavicular nodes, at 2 Gy per day; total dose was 44 Gy. The areas involved by tumor were boosted with 10 Gy more. Prophylactic cranial irradiation (PCI) was started at the same time with 15 treatments of 2.75 Gy. A 2-week rest period was instituted after the first 11 treatments. Chemotherapy (CT) was given from day 1 which consisted of 5-Flourouracil, 500 mg./M2, (bolus day 1 and 8) Vincristine, 1 mg./M2, and Mitomycin C, 5 mg./M2 both given on day 1. Cycles were repeated at 28 day intervals for 3 cycles and at 6 week intervals for 5 more cycles, or until progression, with persistent disease. Eight cases (33%) achieved complete response (CR), and 5 (21%) partial response (PR). Overall median survival was 37 weeks and 2 years survival was 8%. CR patients had the best chance for long-term survival. Relapses were evenly distributed between extra and intrathoracic sites, with the latter even between the inside and outside the RT field. No patient died with clinical evidence of metastasis to the brain (MB), although one was found to have MB at autopsy. Toxicity was severe in 7 cases (29%) and 2 deaths are considered toxicity related. When comparing these results to those from the literature, we found this protocol has achieved a slightly higher CR rate than what is expected with RT alone, without survival improvement. As CR patients have the best prognosis, simultaneous CT-RT might offer some promise, but at the expense of increased toxicity. PCI was effective in preventing or delaying MB, and thus deserves further investigation. We should caution that the study of possible long-term effects of PCI could not be assessed because of the short median survival of the patients. It is possible that a less aggressive time-dose fractionation to the brain might be as effective as the one used in this protocol.

An electron beam pseudoarc technique for irradiation of large areas of chest wall and other curved surfaces.

An electron beam technique has been developed for the treatment of large areas of the chest wall and other curved surfaces employing the stationary field electron beam mode ordinarily available on a linear accelerator. The technique simulates an arc through the use of multiple fixed fields. The electron collimator is not used. Field shaping is achieved through the combined effects produced by the photon jaw settings, the arc limits, and secondary lead shielding on the patient's skin. Thus, there is no limitation on the circumferential extent of the field size that can be used. Electron beam energies of 6 MeV, 9 MeV, 12 MeV, 15 MeV and 18 MeV have been studied. Our findings indicate that, for these energies, this technique produces isodose curves parallel to the cylindrical surface at all depths beyond maximum build-up. This paper discusses the physical characteristics of the single beams, the degree of dose homogeneity achieved with the multiple fields, and the dosimetry technique developed to implement the therapy.

Advantages and limitations of computed tomography scans for treatment planning of lung cancer.

Forty-five Chest computed tomography (CT) scans performed on patients with lung carcinoma (LC) were evaluated in an attempt to understand the pattern of intrathoracic tumor spread and the advantages and limitations this technique offers for treatment planning when compared to planning done by conventional X rays. The following findings can help treatment planning. (1) When regular X rays do not show tumor location (i.e., hemithorax opacification), CT scan will show it in 68% of patients. If regular X rays show a well localized mass, unsuspected tumor extensions were disclosed in 78% of these patients. Hence, CT scans should be done in all LC patients prior to treatment planning; (2) Mediastinal masses frequently spread anteriorly toward the sternum and posteriorly around the vertebral bodies toward the cord and costal pleura. This should be considered for radiotherapy boost techniques; (3) Lung masses spread in one third of cases toward the lateral costal pleura. Thus, the usual 1-2cm of safety margin around the LC are not sufficient in some cases; (4) Tumor size can appear much smaller in regular X rays than in CT scans. Hence, CT scans are necessary for accurate staging and evaluation of tumor response. Some CT scan limitations are: (1) Atelectasis blends with tumor in approximately half of the patients, thus obscuring tumor boundaries; (2) CT numbers and contrast enhancement did not help to differentiate between these two structures; and (3) Limited definition of CT scan prevents investigation of suspected microscopic spread around tumor masses.

Evaluation of computed tomography numbers for treatment planning of lung cancer.

Computerized tomography numbers (CTN) were evaluated in 32 computerized tomography scans performed on patients with carcinoma of the lung, with the aim of evaluating CTN in normal (lung, blood, muscle, etc) and pathologic tissues (tumor, atelectasis, effusion, post-radiation fibrosis). Our main findings are: 1. Large individual CTN variations are encountered in both normal and pathologic tissues, above and below mean values. Hence, absolute numbers are meaningless. Measurements of any abnormal intrathoracic structure should be compared in relation to normal tissue CTN values in the same scan. 2. Tumor and complete atelectasis have CTN basically similar to soft tissue. Hence, these numbers are not useful for differential diagnosis. 3. Effusions usually have lower CTN and can be distinguished from previous situations. 4. Dosimetry based on uniform lung density assumptions (i.e., 300 mg/cm3) might produce substantial dose errors as lung CTN exhibit very large variations indicating densities well above and below this value. 5. Preliminary information indicates that partial atelectasis and incipient post-radiation fibrosis can have very low CTN. Hence, they can be differentiated from solid tumors in certain cases, and help in differential diagnosis of post radiation recurrence within the radiotherapy field versus fibrosis.

Outcome of prophylactic and therapeutic cranial irradiation in disseminated small cell lung carcinoma: a Southwest Oncology Group Study.

The issue whether cranial radiotherapy (RT) should be used prophylactically (PCI) or therapeutically (TCI) in small cell lung carcinoma (SCLC) is considered controversial by some oncologists. Trying to clarify this issue we have performed a retrospective analysis of a Southwest Oncology Group (SWOG) protocol for disseminated SCLC. Three Hundred and seventy-seven cases had no evidence of metastases to the brain (MB). One hundred and forty four of those had PCI. Seventy one cases were diagnosed of MB, and 64 received TCI. We confirmed previous reports showing a low percentage of brain relapse with PCI (around 5%), with minimal immediate morbidity. We also confirmed a high percentage of objective response (90%) with TCI, (although we had no response information in 40% of them) with long duration of response of 33 weeks. Brain relapse after TCI was only 18%. Only long-term survivors had brain relapse as survival of relapsing patients was longer than those without brain relapse (45 weeks versus 33 weeks, p = 0.06). However, 20 (31%) of the 65 with initial MB died within 6 weeks of registration, some without completing RT to brain. In the majority, cause of death was considered related directly to brain damage, or indirectly as sepsis developed in patients whose poor performance status was considered to be caused by their brain symptoms. When comparing patients with and without MB, the former had (a) worse survival (24 versus 32 weeks, p = 0.02) and (b) higher proportion of patients with poor initial performance status (50% versus 34%, p = 0.04). Although the possibility of long-term morbidity with PCI is deterring some oncologists from recommending it, our data show that MB creates a real chance for immediate morbidity and this should not be ignored. The pros and cons of both approaches and some new recommendations for PCI are discussed.

Is it worthwhile to treat Peyronie disease?

Several articles describing the natural history of Peyronie disease have shown that untreated patients seem to have spontaneous improvement. It has been suggested that this could be the reason for the success of so many different methods. A review of the literature and of our previous experience has been done, trying to clarifying this issue. Our findings indicate that although treatment does not increase appreciably the percentages of amelioration of symptoms over the spontaneous evolution, it accelerates the improvement. Analysis is made of several factors which we have found to be important when making a decision for treatment: type of symptoms, psychologic impact of them, possible complications of the different therapy methods, and time interval from beginning of symptoms to treatment. The question of the worthiness of treating Peyronie disease does not have a single answer. We believe there are definite indications and several factors to be considered.

Evaluation and radiotherapy implications of chest relapse patterns in small cell lung carcinoma treated with radiotherapy-chemotherapy: study of 34 cases and review of the literature.

Evaluation and radiotherapy implications of chest relapse patterns in small cell lung carcinoma treated with chemotherapy and radiotherapy to the chest and brain. Emphasis was placed on analysis of patterns of chest disease relapse, chest complications, and sites of initial chest disease relapse in relation to volume treated by radiation. These results were compared with published reports. Of 17 cases with disease limited to the chest (LD), nine (53%) died of chest related complications, seven of these (41%) with chest disease recurrence. However, in five of these seven cases (72%), recurrences appeared initially outside the irradiated volume, in spite of 1-2 cm of safety margin, mostly in the ipsilateral lung, while the primary was without evidence of growth. Hence, chest disease relapse does not necessarily mean radiotherapy failure, as only 2 of the 17 cases (12%) had definite tumor growth in the irradiated field. This point is not properly emphasized in the literature, where marked discrepancies among authors reporting chest disease relapses are present. We elaborate about factors that will affect results, like frequency of follow-up x-rays, tumor size, site of chest disease relapse, and criteria to define tumor relapse. More autopsy and chest diagnostic studies are needed to investigate patterns of tumor spread within the lung. Survival alone is too broad a factor to measure the impact of radiotherapy in treatment. We need more understanding of the mechanisms of chest disease relapse to obtain a better design of radiotherapy ports. Systemic disease was the main cause of death in 17 patients with extensive small cell lung carcinoma, and routine chest irradiation cannot be justified although it might be of help for chemotherapy responders who are expected to have long survival.

The role of radiotherapy in the management of malignant hemangiopericytoma: report of eleven new cases and review of the literature.

The response of hemangiopericytoma to radiation therapy was studied in 11 patients treated at Memorial Hospital. Response of greater or lesser degree was noted in 26 of 29 radiation therapy courses administered. These included 14 instances of complete tumor regression. Dose and tumor size were the main factors influencing response. The tumors tend to regress slowly and incompletely; yet effective relief of symptoms and long term local control (average duration 27 months) usually was achieved. These results and those reported by others believe the alleged inefficacy of radiation therapy in the management of these tumors. Palliative radiation therapy seems to be worthwhile even in advanced cases. Because of the high rate of local recurrence after surgical excision, treatment strategies combining local excision of large primary tumors with wide-field, high-dose radiation therapy are worthy of trial.

Correlation between initial salivary flow rate and radiation dose in the production of xerostomia.

Dose and initial flow rate are two of several factors that influence the outcome of xerostomia when irradiating head and neck tumors. These two parameters were analysed in 11 irradiated patients where most salivary glands were in the radiation field. Unstimulated whole saliva samples were collected before, during and after the irradiation. The results indicate a statistically significant linear correlation between initial saliva flow rate and the accumulated dose causing irreversible xerostomia. This phenomenon is explained. A diagram is made that could be used (in head and neck tumors where one side could be spared) as a indicator of the maximum dose the salivary glands in the contralateral non-involved side can receive before reaching irreversible dryness.

[IgA deficiency] / Deficiência de IgA.

OBJECTIVE: The studies about immunoglobulin A (IgA) deficiencyin the clinical, laboratorial and terapeutic aspects. METHODS: Bibliografic review of the last ten years about thesubject by Medline system and direct research. RESULTS AND CONCLUSIONS: IgA deficiency is the most frequent primary immunodeficiency, with the average prevalence of 1:700and must be studied in its clinical, laboratorial and terapeutic aspectsby pediatrician and other specialists. The clinical characteristics ofthe total and partial immunodeficiency must be known, so as thecomplications and laboratory techniques for determine accurate diagnosis and prognostic.

Simultaneous combination radiotherapy and multidrug chemotherapy for stage III and stage IV squamous cell carcinoma of the head and neck.

Combined simultaneous radiotherapy and multidrug chemotherapy have been utilized in an attempt to eradicate or shrink tumors of the head and neck area in advanced stages to allow subsequent surgical extirpation. Thirty-six patients (1 stage II; 11 stage III; 24 stage IV; 1 unknown primary) were treated with simultaneous radiotherapy and fractionalized doses of bleomycin, adriamycin, and 5-fluorouracil. Thirty of 36 patients completed the treatment schedule. Twenty-nine of 30 (97%) had a 75% or greater response to treatment; 20/30 (66%) had 100% response; 9/30 (30%) had 75% response; and 1/30 had 50% response. Of the 30 patients completing the regimen, 19/30 (63%) are alive three to 27 months later, and 12 (40%) of these have no evidence of disease. Six patients died within four months of initiation of therapy, mostly from complications of their disease. This treatment regimen appears effective in the control of locoregional disease or to produce enough shrinkage of tumor to allow subsequent surgical extirpation.

Alterations in whole saliva flow rate induced by fractionated radiotherapy.

Sequential changes in flow rate of whole saliva are detailed in 13 patients. Samples were collected without exogneous stimulation during a course of fractionated radiotherapy involving major portions of the salivary glands. Flow rate decreased markedly during the initial 3 treatment days and gradually thereafter until a minimal flow rate was reached. Early in the treatment, variable degrees of recovery were seen on Mondays following a weekend (Friday-Sunday) without treatment. After a minimal flow rate was reached, no such recovery was observed. Radiation needed to produce minimal flow varied from 450 to 4,050 rad. Patients with higher initial flow rates required higher dosages to reach the minimum. No return of secretory function was noted after extended periods of time.