Pelvic inflammatory disease (PID) from Chlamydia trachomatis versus PID from Neisseria gonorrhea: from clinical suspicion to therapy.

Pelvic inflammatory disease (PID) is the most significant complication of sexually transmitted infections in childbearing-age women and it represents an important public health problem because of its long-term sequelae (chronic pelvic pain, tubal infertility, ectopic pregnancy). Prior to the mid 1970s PID was considered a monoetiologic infection, due primarily to Neisseria gonorrhea. Now it is well documented as a polymicrobial process, with a great number of microrganisms involved. In addition to Neisseria gonorrhea and Chlamydia trachomatis, other vaginal microrganisms (anaerobes, Gardnerella vaginalis, Haemophilus influenzae, enteric Gram negative rods, Streptococco agalactie, Mycoplasma genitalium) also have been associated with PID. There is a wide variation in PID clinical features; the type and severity of symptoms vary by microbiologic etiology. Women who have chlamydial PID seem more likely than women who have gonococcal PID to be asymptomatic. Since clinical diagnosis is imprecise, the suspicion of PID should be confirmed by genital assessment for signs of inflammation or infection, blood test and imaging evaluation. Laparoscopic approach is considered the gold standard. According to the polymicrobial etiology of PID, antibiotic treatment must provide broad spectrum coverage of likely pathogens. Early administration of antibiotics is necessary to reduce the risk of long-term sequelae.

[Proteomic applications in gynecology-obstetrics]. / Applicazioni della proteomica in ambito ginecologico-ostetrico.

Proteomics has recently emerged as a powerful approach both for discovering biomarkers as well as for understanding the physiopathology of unclear gynecological-obstetrical disorders. Currently, several biological fluids and fetal tissues were successfully tested, including maternal plasma, amniotic fluid, cervical-vaginal fluid, urine, saliva, placental trophoblast, amnio-chorionic membranes and cord blood. The potential of proteomics on the polycystic ovary syndrome (PCOS) involves biomarkers discovery for a more accurate diagnosis of the syndrome and identification, within the patients with PCOS, those who respond more easily to treatment and those who will be at increased risk for future metabolic complications. The proteomic approach applied to patients with endometriosis would allow not only a non-invasive early diagnosis, but also a staging of the disease and a prediction of infertility risk. Proteomics also involves oncological field, in order to discover biomarkers that allow early diagnosis and prognosis of female genital malignancies. In addition to this, proteomics could be used to understand and predict obstetrical complications such as recurrent spontaneous abortion, preterm birth and preeclampsia. However, further studies are needed on a larger cohort of patients to introduce these biomarkers in clinical practice.

Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer.

BACKGROUND: Regionally advanced, surgically unresectable non-small-cell lung cancer represents a disease with an extremely poor prognosis. External-beam irradiation to the primary tumor and regional lymphatics is generally accepted as standard therapy. The use of more aggressive radiation regimens and the addition of cytotoxic chemotherapy to radiotherapy have yielded conflicting results. Recently, however, results from clinical trials using innovative irradiation delivery techniques or chemotherapy before irradiation have indicated that patients treated with protocols that incorporate these modifications may have higher survival rates than patients receiving standard radiation therapy. PURPOSE: On the basis of these results, the Radiation Therapy Oncology Group (RTOG)-Eastern Cooperative Oncology Group (ECOG) elected to conduct a phase III trial comparing the following regimens: 1) standard radiation therapy, 2) induction chemotherapy followed by standard radiation therapy, and 3) twice-daily radiation therapy. METHODS: Patients with surgically unresectable stage II, IIIA, or IIIB non-small-cell lung cancer were potential candidates. Staging was nonsurgical. Patients were required to have a Karnofsky performance status of 70 or more and weight loss less than 5% for 3 months prior to entry into the trial, to be older than 18 years of age, and to have no metastatic disease. Of the 490 patients registered in the trial, 452 were eligible. The disease in 95% of the patients was stage IIIA or IIIB. More than two thirds of the patients had a Karnofsky performance status of more than 80. Patients were randomly assigned to receive either 60 Gy of radiation therapy delivered at 2 Gy per fraction, 5 days a week, over a 6-week period (standard radiation therapy); induction chemotherapy consisting of cisplatin (100 mg/m2) on days 1 and 29 and 5 mg/m2 vinblastine per week for 5 consecutive weeks beginning on day 1 with cisplatin, followed by standard radiation therapy starting on day 50; or 69.6 Gy delivered at 1.2 Gy per fraction twice daily (hyperfractionated radiation therapy). RESULTS: Toxicity was acceptable, with four treatment-related deaths. Three patients subsequently died of chronic pulmonary complications. Compliance with protocol treatment was acceptable. One-year survival (%) and median survival (months) were as follows: standard radiation therapy--46%, 11.4 months; chemotherapy plus radiotherapy--60%, 13.8 months; and hyperfractionated radiation therapy--51%, 12.3 months. The chemotherapy plus radiotherapy arm was statistically superior to the other two treatment arms (logrank P = .03). CONCLUSIONS: In "good-risk" patients with surgically unresectable non-small-cell lung cancer, induction chemotherapy followed by irradiation was superior to hyperfractionated radiation therapy or standard radiation therapy alone, yielding a statistically significant short-term survival advantage.

Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection.

To evaluate the role of mediastinal irradiation (RT) following surgery for invasive thymomas, a clinical and pathologic review of 117 patients with the diagnosis of thymoma was completed. Fourteen cases were excluded because of the lack of histologic criteria for a thymic tumor, and the remaining 103 were classified according to a staging system as follows: stage I, completely encapsulated (43); stage II, extension through the capsule or pericapsular fat invasion (21); stage III, invasion of adjacent structures (36); and stage IV, thoracic dissemination or metastases (3). The 5-year actuarial survival and relapse-free survival rates were 67% and 100% for stage I, 86% and 58% for stage II, and 69% and 53% for stage III. No recurrences occurred among stage I patients after total resection without RT. However, eight of 21 patients with invasive (stage II or III) thymomas had mediastinal recurrence as the first site of failure following total resection without RT. The 5-year actuarial mediastinal relapse rate of 53% in this group compares unfavorably with the mediastinal relapse rate seen among stage II or III cases following total resection with RT (0%) or following subtotal resection/biopsy with RT (21%). Despite attempted salvage therapy, five of eight patients with mediastinal relapse following total resection alone died of progressive disease. No significant difference was observed in the local relapse rate, overall relapse rate, or survival between those patients undergoing biopsy and RT v subtotal resection and RT for invasive thymomas (stages II and III). Total resection alone appears to be inadequate therapy resulting in an unacceptably high local failure rate with poor salvage therapy results.

Alternating chemotherapy and twice-daily thoracic radiotherapy in limited-stage small-cell lung cancer: a pilot study of the Eastern Cooperative Oncology Group.

PURPOSE: This pilot study was undertaken to determine the efficacy and feasibility of alternating cisplatin and etoposide with multiple daily fractions of thoracic radiotherapy (TRT) in patients with limited-stage small-cell lung cancer (SCLC). PATIENTS AND METHODS: Thirty-four SCLC patients received four courses of cisplatin (30 mg/m2/d x 3) plus etoposide (120 mg/m2/d x 3) (PE) every 3 weeks. TRT was administered twice daily (1.5 Gy per fraction) for 5 consecutive days in the week after cycles 1, 2, and 3 of chemotherapy (total TRT dose, 45 Gy). Patients who achieved a complete response (CR) received one course of late-intensification (LI) treatment consisting of cyclophosphamide (4 g/m2) and etoposide (900 mg/m2). Prophylactic cranial irradiation (PCI) was optional. RESULTS: Nineteen of 32 assessable patients achieved a CR (59%) and 12 had a partial response (38%), for an overall response rate of 97% (95% confidence interval [CI], 84% to 99%). Median survival was 18 months, while 2-year progression-free survival was 47%. Leukopenia < or = 1,000/microL occurred in 12% of induction treatment cycles. Severe esophagitis was uncommon. Pulmonary fibrosis that was asymptomatic or minimally symptomatic was observed in eight patients (25%). There was one episode of adult respiratory distress syndrome (ARDS) during LI chemotherapy. Life-threatening neutropenia (< or = 500/microL) developed in all patients who underwent LI chemotherapy, with a median duration of 10 days (range, 8 to 19). Two patients died of sepsis during LI chemotherapy. CONCLUSION: Alternating PE and TRT as performed in this trial is an effective brief induction regimen for limited-stage SCLC. However, this particular regimen did not appear to be substantially different in terms of efficacy or toxicity compared with regimens using concurrent chemotherapy and standard-fraction TRT. LI chemotherapy was associated with unacceptable toxicity and did not appear to have a favorable impact on survival.

Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma.

PURPOSE: A pilot study of 43 patients with potentially resectable esophageal carcinoma treated with an intensive regimen of preoperative chemoradiation with cisplatin, fluorouracil, and vinblastine before surgery showed a median survival of 29 months in comparison with the 12-month median survival of 100 historical controls treated with surgery alone at the same institution. We designed a randomized trial to compare survival for patients treated with this preoperative chemoradiation regimen versus surgery alone. MATERIALS AND METHODS: One hundred patients with esophageal carcinoma were randomized to receive either surgery alone (arm I) or preoperative chemoradiation (arm II) with cisplatin 20 mg/m2/d on days 1 through 5 and 17 through 21, fluorouracil 300 mg/m2/d on days 1 through 21, and vinblastine 1 mg/m2/d on days 1 through 4 and 17 through 20. Radiotherapy consisted of 1.5-Gy fractions twice daily, Monday through Friday over 21 days, to a total dose of 45 Gy. Transhiatal esophagectomy with a cervical esophagogastric anastomosis was performed on approximately day 42. RESULTS: At median follow-up of 8.2 years, there is no significant difference in survival between the treatment arms. Median survival is 17.6 months in arm I and 16.9 months in arm II. Survival at 3 years was 16% in arm I and 30% in arm II (P = .15). This study was statistically powered to detect a relatively large increase in median survival from 1 year to 2.2 years, with at least 80% power. CONCLUSION: This randomized trial of preoperative chemoradiation versus surgery alone for patients with potentially resectable esophageal carcinoma did not demonstrate a statistically significant survival difference.

Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small-cell lung cancer: mature results of Southwest Oncology Group phase II study 8805.

PURPOSE: To assess the feasibility of concurrent chemotherapy and irradiation (chemoRT) followed by surgery in locally advanced non-small-cell lung cancer (NSCLC) in a cooperative group setting, and to estimate response, resection rates, relapse patterns, and survival for stage subsets IIIA(N2) versus IIIB. PATIENTS AND METHODS: Biopsy proof of either positive N2 nodes (IIIAN2) or of N3 nodes or T4 primary lesions (IIIB) was required. Induction was two cycles of cisplatin and etoposide plus concurrent chest RT to 45 Gy. Resection was attempted if response or stable disease occurred. A chemoRT boost was given if either unresectable disease or positive margins or nodes was found. RESULTS: The median follow-up time for 126 eligible patients [75 stage IIIA(N2) and 51 IIIB] was 2.4 years. The objective response rate to induction was 59%, and 29% were stable. Resectability was 85% for the IIIA(N2) group eligible for surgery and 80% for the IIIB group. Reversible grade 4 toxicity occurred in 13% of patients. There were 13 treatment-related deaths (10%) and 19 others (15%) died of causes not related to toxicity or tumor. Of 65 relapses, 11% were only locoregional and 61% were only distant. There were 26 brain relapses, of which 19 were the sole site or cause of death. There was no survival difference (P = .81) between stage IIIA(N2) versus stage IIIB (median survivals, 13 and 17 months; 2-year survival rates, 37% and 39%; 3-year survival rates, 27% and 24%). The strongest predictor of long-term survival after thoracotomy was absence of tumor in the mediastinal nodes at surgery (median survivals, 30 v 10 months; 3-year survival rates, 44% v 18%; P = .0005). CONCLUSION: This trimodality approach was feasible in this Southwest Oncology Group (SWOG) study, with an encouraging 26% 3-year survival rate. An Intergroup study is currently being conducted to determine whether surgery adds more to the risk or to the benefit of chemoRT.

Dose escalation in non-small-cell lung cancer using three-dimensional conformal radiation therapy: update of a phase I trial.

PURPOSE: High-dose radiation may improve outcomes in non-small-cell lung cancer (NSCLC). By using three-dimensional conformal radiation therapy and limiting the target volume, we hypothesized that the dose could be safely escalated. MATERIALS AND METHODS: A standard phase I design was used. Five bins were created based on the volume of normal lung irradiated, and dose levels within bins were chosen based on the estimated risk of radiation pneumonitis. Starting doses ranged from 63 to 84 Gy given in 2.1-Gy fractions. Target volumes included the primary tumor and any nodes >or= 1 cm on computed tomography. Clinically uninvolved nodal regions were not included purposely. More recently, selected patients received neoadjuvant cisplatin and vinorelbine. RESULTS: At the time of this writing, 104 patients had been enrolled. Twenty-four had stage I, four had stage II, 43 had stage IIIA, 26 had stage IIIB, and seven had locally recurrent disease. Twenty-five received chemotherapy, and 63 were assessable for escalation. All bins were escalated at least twice. Although grade 2 radiation pneumonitis occurred in five patients, grade 3 radiation pneumonitis occurred in only two. The maximum-tolerated dose was only established for the largest bin, at 65.1 Gy. Dose levels for the four remaining bins were 102.9, 102.9, 84 and 75.6 Gy. The majority of patients failed distantly, though a significant proportion also failed in the target volume. There were no isolated failures in clinically uninvolved nodal regions. CONCLUSION: Dose escalation in NSCLC has been accomplished safely in most patients using three-dimensional conformal radiation therapy, limiting target volumes, and segregating patients by the volume of normal lung irradiated.

Randomized study of CODE versus alternating CAV/EP for extensive-stage small-cell lung cancer: an Intergroup Study of the National Cancer Institute of Canada Clinical Trials Group and the Southwest Oncology Group.

PURPOSE: To determine whether an intensive weekly chemotherapy regimen plus thoracic irradiation is superior to standard chemotherapy in the treatment of extensive-stage small-cell lung cancer (ESCLC). PATIENTS AND METHODS: Patients with ESCLC were considered eligible for the study if they were younger than 68 years, had a performance status of 0 to 2, and were free of brain metastases. Patients were randomized to receive cisplatin, vincristine, doxorubicin, and etoposide (CODE) or alternating cyclophosphamide, doxorubicin, vincristine/etoposide and cisplatin (CAV/EP). Consolidative thoracic irradiation and prophylactic cranial irradiation were given to patients responding to CODE and according to investigator discretion on the CAV/EP arm. RESULTS: The fidelity of drug delivery on both drug regimens was equal, and more than 70% of all patients received the intended protocol chemotherapy. Although rates of neutropenic fever were similar, nine (8.2%) of 110 patients on the CODE arm died during chemotherapy, whereas one (0.9%) of 109 patients died on the CAV/EP arm. Response rates after chemotherapy were higher (P =.006) with CODE (87%) than with CAV/EP (70%). However, progression-free survival (median of 0.66 years on both arms) and overall survival (median, 0.98 years for CODE and 0. 91 years for CAV/EP) were not statistically different. CONCLUSION: The CODE regimen increased two-fold the received dose-intensity of four of the most active drugs in small-cell lung cancer compared with the standard CAV/EP regimen while maintaining an approximately equal total dose. Despite supportive care (but not routine prophylactic use of granulocyte colony-stimulating factor), there was excessive toxic mortality with the CODE regimen. The response rate with CODE was higher than that of CAV/EP, but progression-free and overall survival were not significantly improved. In view of increased toxicity and similar efficacy, the CODE chemotherapy regimen is not recommended for treatment of ESCLC.

Radiation and chemotherapy sensitizers and protectors.

Radiosensitizers and radioprotectors are part of the chemical modifier approach to cancer therapy whereby the state of the tumor cells and/or normal tissues are modified such that a therapeutic gain is achieved using conventional radiation or chemotherapy. Radiosensitization can be achieved by the use of oxygen-mimetic compounds, agents that alter DNA sensitivity to irradiation, maneuvers that alter DNA repair processes, and manipulation of tissue oxygenation. Standard chemotherapeutic agents such as cisplatin can be utilized in a manner that optimizes the radiosensitization properties. Protection and sensitization can occur by altering the thiol status of the cell. The chemical modifiers field is both developing novel approaches to cancer treatment and increasing the understanding of basic cancer biology.

Counterpoint: better radiation treatment of non-small cell lung cancer using new techniques without elective nodal irradiation.

The treatment of non-small cell lung cancer has continued to evolve with the advent of improved staging technologies, chemotherapeutic agents, and methods of radiation delivery. Treatment of clinically uninvolved, regional lymph nodes historically has been delivered in the attempt to cover unseen disease, reduce regional failure, and improve survival. None of these suppositions has been tested nor are they supported by data. With enhanced staging using modalities like positron emission tomography and esophageal ultrasonography, treatment portals can be designed to encompass known disease with greater accuracy and confidence. Data for early-stage non-small cell lung cancer is now increasing and strongly suggest that eliminating elective nodal irradiation does not result in a high incidence of nodal relapse and does not compromise survival. Three-dimensional conformal radiotherapy incorporates better targeting and beam directions to effect smaller treatment volumes that include only clinically evident disease. It provides treatment techniques that maximize tumor dose and minimize normal tissue toxicity. Using smaller fields that do not incorporate elective nodal regions may allow higher doses, and these may help improve local control and survival in a disease where current results are unacceptable.

The treatment of limited small cell lung cancer: a report of the progress made and future prospects.

The improvements in the treatment of small cell lung cancer over the last 30 years have been realised by understanding that it is a systemic disease, but that areas of bulk and sanctuary require a complementary therapy. Despite successful strategies using combinations and thoracic radiotherapy, there remains uncertainty about what the best regimens are, their timing and their intensity. However, earlier concurrent therapy and rather brief intense chemotherapy and radiotherapy seem to produce the best results in moderately fit patients of all ages. How to select the fit patients and what to do about the less fit ones remains controversial and have economic consequences for governments and payers. Despite a meta-analysis demonstrating the success of prophylactic cranial irradiation (PCI), doubts linger about its safety, despite nothing more than anecdotal evidence from a previous era. The role of surgery continues to be explored, more in Europe than North America or Asia. Strategies for treatment of minimum residual disease seem a focus. New drugs, molecular targeted therapy, immunotherapy and other molecular therapies offer promise and theory, but there is little evidence about their place in the treatment protocols of today.

The integration of platinum and radiotherapy in the treatment of lung cancer.

Combined-modality therapy in lung cancer is a common practice throughout the world. The use of radiochemotherapy appears to be firmly established in the treatment of small cell lung cancer, but the role of prophylactic cranial irradiation remains undecided. Many recommend its use in the treatment of non-small cell lung cancer as well, but no facts exist to support this position. Because of poor long-term outcome and high frequency of systemic relapse, integration of chemotherapy for the treatment of non-small cell lung cancer is becoming more prevalent. This article discusses methods of integration, the problems of combined- modality toxicity, recent trials, and reports of multimodal therapy in lung cancer. The advantages of certain regimens of chemotherapy and new methods of radiotherapy are also discussed.

Platinum combined with radiation therapy in small cell lung cancer: focusing like a laser beam on crucial issues.

The addition of radiotherapy to combination chemotherapy has been shown to improve survival for patients with limited small cell lung cancer (SCLC). Although SCLC is very sensitive to radiotherapy, the impact of radiation may be confounded by interaction among various radiotherapy factors or by the chemotherapeutic agents used in combination. The potential effects of such radiation factors as dose, volume, fractionation, sequence with chemotherapy, and timing (early v late), as well as choice of chemotherapy, therefore must be carefully considered when designing or comparing clinical trials of combined modality therapy for SCLC. The combination of thoracic radiotherapy plus platinum-based chemotherapy currently represents the cornerstone of such combination treatment for SCLC. Many questions remain, however, and it is hoped that new trials will be designed to focus more precisely on unsettled issues.

The evolving role of radiation therapy in the treatment of locally advanced lung cancer.

RT has been used routinely in the treatment of NSCLC and SCLC for the past several decades. Although largely considered a palliative treatment by most oncologists, there is increasing evidence that RT, when combined with cisplatin-based chemotherapy or given by altered fractionation, may improve the survival in NSCLC. Three large randomized trials have now shown that RT plus a cisplatin-based combination or cisplatin alone prolongs patient survival. Studies of hyperfractionation and accelerated hyperfractionation have also shown promise and are being tested in randomized trials worldwide. The results from these trials must be assessed against ongoing radiation dose escalation studies using new treatment planning technologies, albeit still in their infancy. These trials are discussed in this report. Systemic therapy is the cornerstone of treatment for SCLC. Although the value of RT was hotly debated during the 1970s and 1980s, it is now well established that RT improves survival when combined with chemotherapy in limited stage patients. Despite this advancement, other issues (such as timing or sequencing of modalities, radiation dose, fractionation, and treatment volume), remain unsettled. Randomized trials designed to address these important issues are in progress.

Gemcitabine and radiation therapy for non-small cell lung cancer.

Patients with stage III non-small cell lung cancer (NSCLC) frequently progress either within the irradiated field or systemically, due to uncontrolled microscopic dissemination present before the time of initial diagnosis. The use of combined modality therapy has led to improved survival rates in recent years. In particular, the use of cisplatin and vinblastine as induction chemotherapy is supported by two large randomized clinical trials. Nevertheless, the large majority of patients still die of progressive disease, thus providing a rationale for the integration of new active agents into the overall treatment plan of these patients. Gemcitabine has demonstrated significant single-agent activity in NSCLC. In addition, preclinical and early clinical data indicate that it is a powerful radiation enhancer. Clinical trials investigating this drug with concurrent radiation therapy in NSCLC are reviewed.

Thoracic radiotherapy variables: influence on local control in small cell lung cancer limited disease.

In limited small cell lung cancer (LSCLC), the high local failure rate of chemotherapy by itself (60-100%) and with the addition of external beam radiotherapy (approximately 30%) has led to investigation of methods to improve local control. To that end, we integrated Platinum 60 mg/m2, d. 1, 22 and Etoposide 120 mg/m2, d. 4, 6, & 8; 25, 27 & 29 with concurrent twice-daily 150 cGy (total dose: 4500 cGy). Of 32 consecutively referred patients, 4 with variant histology, 31 were evaluable for toxicity, response, and survival. Two of 4 variant histology patients responded, and 27 of 27 pure small cell responded, p = 0.005. CT scans were inaccurate at forecasting survival. Of 17/32 patients considered "positive," 59% of these were survivors; of those considered "negative," 47% were survivors, p = N.S. Radiation portals were volumetrically conservative; the supraclavicular fossa was included infrequently and the contralateral hilum not at all. Local failure occurred in only 1/27 patients (4%). All four variant patients failed locally, p = 0.001. With a median follow-up of 43 months, the actuarial disease-free survival remains nearly 50%. Variant histology is more predictive of local control than the physical factors of dose or volume.

Palliative radiotherapy for metastatic malignant melanoma: brain metastases, bone metastases, and spinal cord compression.

The records of all patients receiving palliative radiotherapy for malignant melanoma metastatic to brain, to bone, or with spinal cord compression were reviewed. The median survival of 77 patients with brain metastases from the initiation of radiotherapy was 14 weeks. A statistically improved survival was observed only in the 10 patients who underwent subtotal to total resection of a solitary brain metastasis prior to radiotherapy (median = 36 weeks). No improved survival was observed in the 12 patients with a solitary brain metastasis treated by radiotherapy alone (median = 16 weeks). Multivariate analysis revealed that fraction size, total dose, patient age, sex, and duration of the interval between initial diagnosis and appearance of brain metastases did not significantly influence survival, but the use of chemotherapy was associated with a decreased survival. Twenty six patients with symptomatic and radiographic evidence of 39 bone metastases showed a palliative response rate of 85%. 18 of 20 bony lesions treated with high-dose-per-fraction (greater than or equal to 400 cGy) and 15 of 19 bony lesions treated with conventional fractionation (less than or equal to 300 cGy) were palliated. Total dose, patient age, sex, interval between initial diagnosis of malignant melanoma and the appearance of bone metastases, prior or concurrent chemotherapy, or lesion location did not significantly influence palliation. Seventeen patients were identified with symptomatic and myelographic evidence of spinal cord compression. Complete palliation was observed in 47% (8/17) and partial palliation was observed in 24% (4/17). The overall palliation response rate for neurologic symptoms due to spinal cord compression of 71% appeared to be independent of fraction size and total dose.

A preliminary report: concurrent twice-daily radiotherapy plus platinum-etoposide chemotherapy for limited small cell lung cancer.

From July 1984 through March 1987 23 patients with small cell lung cancer have entered a trial at the University of Pennsylvania. Concurrent Platinum (DDP) Etoposide (VP-16) chemotherapy and twice-daily, 150 cGy radiotherapy to a total dose of 4500 cGy in 3 weeks was used. Besides the twice-daily radiotherapy, multiple field arrangements attempted to minimize normal tissue exposure while concentrating on the target volume. Sophisticated CT-assisted treatment planning employing beams-eye-view technology was used. Esophagitis occurred in 73% (13% severe); hematologic toxicity occurred in 65% (17% WBC less than 1000). Response--100% in pure small cell carcinoma, 91% overall. Median follow-up is 22 months with an actuarial projection of 56% 2-year survival. Median survival is not yet reached. This is a highly effective therapy with substantive but tolerable toxicity. Accrual and follow-up continues. This is a preliminary report. We expect 30 patients before closing the study. A parallel study is underway in the Eastern Cooperative Oncology Group, with a randomized prospective trial in the design stage.

The influence of tumor size and pre-treatment staging on outcome following radiation therapy alone for stage I non-small cell lung cancer.

From 1970 through 1987, 77 patients with Stage I lung cancer were treated with definitive radiation therapy (RT) alone at the Fox Chase Cancer Center or the Hospital of The University of Pennsylvania. All patients had a pathologic diagnosis of non-small cell lung cancer and were not candidates for surgical resection because of premorbid medical problems or patient refusal. The median age was 72 years, although 10 patients were over 80. The histologic cell type was squamous in 44, adenocarcinoma in 15, large cell in 3, adenosquamous in 1, non-small cell in 11, and bronchioli-alveolar in 3. Tumor size was retrievable in 75 patients and 25 were less than or equal to 3 cm, 41 from 3-6 cm, and 9 greater than 6 cm. Diagnostic staging varied during the study period. Twelve patients, evaluated with a CT scan of the chest, including the liver, and a bone scan were classified as having "excellent" staging, 24 patients with conventional tomography, liver-spleen scan and a bone scan had "good" staging, and 41 patients were staged less rigorously. The RT was of megavoltage energy in all patients. The median dose was 60 Gy. The mediastinum was treated in all but eight patients who had poor pulmonary function. Survival was measured from the date of pathologic diagnosis. The actuarial 3-year survival rate of the entire group of patients is 17% with a median survival time of 20 months. Of the 61 deaths, 51 were due to disease and 10 were due to intercurrent disease without evidence of tumor recurrence. The actuarial 3-year disease-specific survival (DSS) was 22%. The 3-year disease-specific survival for patients with tumors less than 3 cm and from 3-6 cm was 30% and 17%, respectively. All nine patients with tumors greater than 6 cm were dead of disease. Local progression occurred in 33 patients, resulting in a 44%, 3-year actuarial freedom from local progression. The median time to local failure was 28 months and there were no local failures after 3 years in the 18 patients eligible for observation beyond this point. Of the patients with "excellent" staging, only 2 of 12 were dead of disease compared with 22 of 24 with "good" staging and 30 of 41 of the remainder. In this large group of Stage I non-small cell lung cancer, thorough pre-treatment staging and smaller tumor size are associated with a more favorable outcome.