Intrathoracic Failure Research Articles

PO-1317 Intrathoracic Failure Pattern in the ES-SCLC Following the 1st-line Immunotherapy

PO-1317 Intrathoracic Failure Pattern in the ES-SCLC Following the 1st-line Immunotherapy

Usefulness of Gastrojejunostomy Prior to Fundoplication in Severe Gastro-Esophageal Reflux Complicating Long-Gap Esophageal Atresia Repair: A Preliminary Study

Background: Gastro-esophageal reflux disease (GERD), requiring surgical correction, and nutritional problems are reported after long-gap esophageal atresia (LGEA) repair and might jeopardize the postoperative course in some babies. We report an exploratory evaluation of the role of transgastric jejunostomy (TGJ) as a temporary nutritional tool before surgery for GERD in LGEA. Methods: Seven infant patients operated on for LGEA with intra-thoracic gastro-esophageal junction (GEJ) and growth failure, requiring improvement in their nutritional profile in anticipation of surgery, were retrospectively evaluated. Post-surgical follow-up, including growth evolution, complications, and parental quality of life (QoL), were considered. Results: The TGJ was placed at a mean age of 8.6 ± 5.6 months. The procedure was uneventful and well-tolerated in all seven cases. At 6.6 ± 2.0 months after TGJ placement, significant weight gain (weight z-score −2.68 ± 0.8 vs −0.9 ± 0.2, p < 0.001) was recorded, allowing the GERD surgery to proceed. A significant difference in hospital admissions between 3 months before and post-TGJ insertion was noted (4.8 ± 0.75 vs. 1.6 ± 0.52, p < 0.01). A significant amelioration of QoL after TGJ placement was also recorded; in particular, the biggest improvements were related to parents’ perceptions of the general health and emotional state of their babies (p < 0.001). Conclusions: The placement of TGJ as a temporary nutritional tool in selected cases of LGEA could improve nutritional conditions and parental QoL before fundoplication, allowing successful surgical treatment of GERD to be carried out.

Durvalumab after concurrent chemotherapy and high-dose radiotherapy for locally advanced non-small cell lung cancer

ABSTRACT The standard of care for stage III non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by durvalumab. Although doses higher than 66 Gy are standard in our center, they were used in only 6.9% of patients in the PACIFIC trial. We report our experience with durvalumab after high-dose radiotherapy. The database of a tertiary hospital for patients with stage III NSCLC who were treated with CRT and adjuvant durvalumab was evaluated. Progression-free survival (PFS), overall survival (OS), and local-regional failure (LRF) were measured from the administration of durvalumab. Thirty-nine patients were included. All were treated with intensity-modulated radiation (mean dose 69.9 Gy); Median follow-up time was 20.4 months (range 1–35.4). At 12 months, PFS was 49%, OS 79%, and LRF 14%. Intrathoracic failure at first progression was demonstrated in 8 (21%) patients. Adverse events requiring corticosteroids occurred in 10(25.6%) patients: pneumonitis – 6 (15.4%), hepatitis – 2 (5.1%), and arthralgia and pericarditis – 1 (2.6%). One patient (2.6%) died of pneumonitis. The occurrence of pneumonitis was significantly associated with lung V5 (55% vs. 42%, p = .04) and V20 (28% vs. 19%, p = .01) and mean lung dose (14.8 Gy vs.11.6 Gy, p = .05). The similar 12-month PFS and OS rates of our cohort and the PACIFIC trial support the use of high-dose radiotherapy in patients with stage III NSCLC. Treatment-related mortality was similar to the PACIFIC results. The intrathoracic failure rate in our cohort was lower than that reported from the PACIFIC trial, suggesting that radiation dose escalation may improve local control.

Outcomes of Stage III NSCLC with occult primary vs. known primary lesions

ObjectivesOccult primary non-small cell lung cancer (OP-NSCLC) involving mediastinal lymph nodes without an identifiable primary tumor is a rare presentation, with little known about how outcomes compare to typical Stage III NSCLC. We reviewed our experience treating OP-NSCLC with definitive radiotherapy and compared outcomes to a contemporary cohort of stage III NSCLC patients. Materials and methodsWe reviewed 605 patients with stage III NSCLC staged with PET-CT and treated with definitive radiotherapy between 1998 and 2013. Overall survival, intrathoracic control, and freedom from distant metastasis were computed using Kaplan-Meier method and logrank comparison. Cox hazard ratios were used to perform univariate and multivariate analyses. ResultsTwenty-one patients were identified with OP-NSCLC (3.5%). Patients with OP-NSCLC, as compared to known primary NSCLC, had significantly better 5-year rates of intrathoracic control (83.5% vs. 24.2%, P < 0.001), freedom from distant metastasis (59.0% vs. 26.3%, P = 0.003), and overall survival (61.6% vs. 15.2%, P < 0.001). Multivariate analyses confirmed occult primary as an independent prognostic factor associated with a 70% reduction in risk of intrathoracic failure, a 55% reduction in risk of distant metastasis, and a 70% reduction in risk of death. ConclusionTo our knowledge, this is the largest reported series of OP-NSCLC and the first to compare it to a contemporary cohort of Stage III NSCLC with known primary lesion. Definitive radiation therapy was associated with favorable locoregional control and survival, particularly compared with typical stage III NSCLC. This difference suggests that occult primary NSCLC may be a distinct entity with different biology than typical NSCLC.

Patterns of initial and intracranial failure in metastatic EGFR-mutant non-small cell lung cancer treated with erlotinib

ObjectivesPatients with metastatic EGFR-mutant (mEGFRmt) NSCLC have favorable survival when treated with erlotinib. We hypothesized that treatment failure in most patients is limited to initial sites of disease, in which case incorporating local therapy such as radiation might further delay progression. We therefore analyzed patterns and predictors of failure in a large cohort of such patients. Materials and methodsWe reviewed 189 patients treated with erlotinib for mEGFRmt NSCLC. We classified first pattern of failure as involving initial sites only (ISF), new sites only (NSF), or the combination (CSF), and used competing-risks regression to identify factors associated with ISF, progression and overall survival (OS). We also separately analyzed intracranial and intrathoracic failure. ResultsOf 171 patients who progressed, 103 (60.2%) had ISF, 30 (17.5%) had NSF, and 38 (22.2%) had CSF. Younger age and lack of initial CNS involvement independently correlated with ISF, with a trend for higher T and N stage. Higher T and N stage was also a significant predictor of progression. Factors predicting shorter OS were female gender, weight loss, initial intracranial involvement, and ≥4 extracranial metastases. Intrathoracic progression was a component of first failure in 61%, and three-year cumulative incidence of brain metastasis was 30%. ConclusionThe main pattern of progression in mEGFRmt NSCLC on erlotinib is in the initial sites of disease. Younger patients and those without brain involvement are particularly likely to develop ISF. This suggests a role for incorporating local therapy into treatment of selected patients with mEGFRmt NSCLC.

Consolidative thoracic radiotherapy for extensive stage small cell lung cancer.

Extensive stage small cell lung cancer (ES-SCLC) represents approximately half of all diagnosed small cell lung cancer worldwide. It is notorious for a high risk of local recurrence although it’s sensitive to chemotherapy. Nearly 90% of intrathoracic failures happen in the first year after diagnosis. The cornerstone of treatment for ES-SCLC is etoposide-platinum based chemotherapy. Consolidative radiotherapy to thorax has diminished the incidence of local relapse, therefore it should be offered to patients with excellent response to induction first-line chemotherapy. This review centers on the clinical evidence for the use of thoracic radiotherapy (TRT) and current modalities of TRT delivery, then tries to determine a feasible way to conduct TRT in a selective group of cases.

Failure Patterns Relative to Radiation Treatment Fields for Stage II–IV Thymoma

The optimal radiation therapy (RT) field design for thymomas remains unclear. Here we report the failure patterns in stage II-IV thymoma after RT at two tertiary referral centers, classified according to the new International Thymic Malignancy Interest Group definitions. We reviewed 156 stage II-IV patients with thymoma treated with definitive (n=24) or adjuvant (n=132) RT. All RT was delivered without elective nodal irradiation (median dose 5040 cGy). Intrathoracic failures were classified as (1) in-field failures (within 100% isodose line [IDL]), (2) marginal recurrences (<100% and ≥50% IDL), and (3) out-of-field failures (outside the 50% IDL). The median follow-up was 61 months. Surgical margins were positive in 39%. The median tumor size was 9 cm. The 5-year cumulative incidence of all intrathoracic failures was 24% (n=34). Failures occurred within the RT field (n=5), marginally (n=1), out-of-field (n=22), and synchronously in- and out-of-field (n=6). The 5-year cumulative incidence of in-field failures was 7%. These were associated with Masaoka stage and tumor size. Macroscopically positive margins were associated with more local failures. Intrathoracic failures occurred most commonly in the pleural space (n=29) and lymph nodes (n=9). Patients with more advanced stage, and those treated with intensity-modulated radiation therapy had more intrathoracic failures. RT dose and chemotherapy did not impact failure patterns. Although there were few in-field failures in patients who received RT for stage II-IV thymomas, a high rate of out-of-field intrathoracic failures still occurred. Further study is necessary to identify treatment approaches that prevent pleural recurrences.

High Dose Involved Field Radiation Therapy as Salvage for Loco-Regional Recurrence of Non-Small Cell Lung Cancer

PurposeTo determine the effectiveness of salvage radiation therapy (RT) in patients with loco-regional recurrences (LRR) following initial complete resection of non-small cell lung cancer (NSCLC) and assess prognostic factors affecting survivals.Materials and MethodsBetween 1994 and 2007, 64 patients with LRR after surgery of NSCLC were treated with high dose RT alone (78.1%) or concurrent chemo-radiation therapy (CCRT, 21.9%) at Samsung Medical Center. Twenty-nine patients (45.3%) had local recurrence, 26 patients (40.6%) had regional recurrence and 9 patients (14.1%) had recurrence of both components. The median RT dose was 54 Gy (range, 44-66 Gy). The radiation target volume included the recurrent lesions only.ResultsThe median follow-up time from the start of RT in survivors was 32.0 months. The rates of in-field failure free survival, intra-thoracic failure free survival and extra-thoracic failure free survival at 2 years were 52.3%, 33.9% and 59.4%, respectively. The median survival after RT was 18.5 months, and 2-year overall survival (OS) rate was 47.9%. On both univariate and multivariate analysis, the interval from surgery till recurrence and CCRT were significant prognostic factors for OS.ConclusionThe current study demonstrates that involved field salvage RT is effective for LRR of NSCLC following surgery.

Stereotactic Body Radiation Therapy for Patients With Lung Cancer Previously Treated With Thoracic Radiation

Stereotactic body radiation therapy (SBRT) provides excellent local control with acceptable toxicity for patients with early-stage non-small cell lung cancer. However, the efficacy and safety of SBRT for patients previously given thoracic radiation therapy is not known. In this study, we retrospectively reviewed outcomes after SBRT for recurrent disease among patients previously given radiation therapy to the chest. A search of medical records for patients treated with SBRT to the thorax after prior fractionated radiation therapy to the chest at The University of Texas M. D. Anderson Cancer Center revealed 36 such cases. The median follow-up time after SBRT was 15 months. The endpoints analyzed were overall survival, local control, and the incidence and severity of treatment-related toxicity. SBRT provided in-field local control for 92% of patients; at 2 years, the actuarial overall survival rate was 59%, and the actuarial progression-free survival rate was 26%, with the primary site of failure being intrathoracic relapse. Fifty percent of patients experienced worsening of dyspnea after SBRT, with 19% requiring oxygen supplementation; 30% of patients experienced chest wall pain and 8% Grade 3 esophagitis. No Grade 4 or 5 toxic effects were noted. SBRT can provide excellent in-field tumor control in patients who have received prior radiation therapy. Toxicity was significant but manageable. The high rate of intrathoracic failure indicates the need for further study to identify patients who would derive the most benefit from SBRT for this purpose.

Radiotherapy and prognostic factors for thymoma: A retrospective study of 175 patients

To assess the factors that predict local control and survival in patients with thymoma treated with adjuvant radiotherapy (RT) and suggest strategies for optimizing adjuvant RT. The study population comprised 47 patients with noninvasive thymoma and 128 patients with invasive thymoma. Treatment was surgery in 175 patients and radiotherapy in 169 patients; 25 patients also received adjuvant chemotherapy. The clinical factors (age, histologic features, stage, presence of myasthenia gravis) and therapeutic factors (extent of operation, irradiation dose, and field size) were retrospectively recorded and accessed using multivariate analysis. The overall survival rate at 5 and 10 years was 86.4% and 80.6%, respectively. Only 2 patients had a relapse in the noninvasive group. None died of thymoma during the study period. The patients with invasive disease had a 5- and 10-year disease-free survival rate of 64.4% and 55.6%, respectively, with 24 intrathoracic failures, 14 extrathoracic failures, and 8 combined failures. The univariate and multivariate analyses showed that Mosaoka stage and extent of resection were the important prognostic factors for patient with invasive thymoma. The 5-year survival rate and local control rate was 96% and 96% for Stage II, 77.8% and 56.4% for Stage III, 56.6% and 42.7% for Stage lVa, and 35.6% and 21.6% for Stage IVb (p < 0.0001 among different stage groups), respectively. The 5-year local control rate in patients with the tumor bed irradiated was 68.2%, comparable to the group treated with an extended RT field (66.6%). Age, histopathologic findings, radiation dose, and presence of myasthenia gravis were not statistically significant prognostic factors. Disease stage and extent of resection affected the prognosis of invasive thymoma patients. Extending the radiation field prophylactically was not associated with greater local control and is of questionable value for patients with invasive thymoma.

Long-term results of a phase III trial comparing once-daily radiotherapy with twice-daily radiotherapy in limited-stage small-cell lung cancer

Purpose This Phase III study was performed to determine whether twice-daily (b.i.d.) radiotherapy (RT) resulted in better survival than once-daily (q.d.) RT for patients with limited-stage small-cell lung cancer (LD-SCLC). Methods and materials A total of 310 patients with LD-SCLC initially received three cycles of etoposide and cisplatin. Subsequently, the 261 patients without significant progression were randomized to two cycles of etoposide and cisplatin plus either q.d. RT (50.4 Gy in 28 fractions) or split-course b.i.d. RT (24 Gy in 16 fractions, a 2.5-week break, and 24 Gy in 16 fractions) to the chest. Patients then received a sixth cycle of etoposide and cisplatin followed by prophylactic cranial RT. Results Follow-up ranged from 4.6 to 11.9 years (median, 7.4 years). The median survival and 5-year survival rate from randomization was 20.6 months and 21% for patients who received q.d. RT compared with 20.6 months and 22% for those who received b.i.d. RT ( p = 0.68), respectively. No statistically significant differences were found in the rates of progression ( p = 0.68), intrathoracic failure ( p = 0.45), in-field failure ( p = 0.62), or distant failure ( p = 0.82) between the two treatment arms. No statistically significant difference was found in the overall rate of Grade 3 or worse ( p = 0.83) or Grade 4 or worse toxicity ( p = 0.95). Grade 3 or worse esophagitis ( p = 0.05) was more common in the b.i.d. arm. Grade 5 toxicity occurred in 4 (3%) of 130 patients who received b.i.d. RT compared with 0 (0%) of 131 who received q.d. RT ( p = 0.04). Conclusion Although this study did not demonstrate an advantage to split-course b.i.d. RT, the long-term survival was favorable, likely reflecting the positive influences of concurrent combined modality therapy and prophylactic cranial RT.

Multiple daily fractionation radiotherapy schedules in lung cancer.

Lung cancer is the number one worldwide cancer killer, and in spite of therapeutic advances, the overall impact on survival has remained very modest. For both small and non-small-cell lung cancer, treatment trends have shifted toward combined-modality approaches, chemotherapy for the control of systemic micrometastases, and radiotherapy for intrathoracic control. However, on both counts, rates of failure remain unacceptably high, and several novel strategies are currently being explored. The use of altered fractionation, including multiple daily fractions, reflects one approach for modifying radiotherapy. The two most common approaches are hyperfractionation and acceleration, the former designed to reduce late normal tissue toxicities and the latter to counteract accelerated tumor repopulation. Recent randomized trials suggest that such approaches may result not only in lowered rates of intrathoracic failure but also in improved survival.

Intra-thoracic failure pattern and survival status following 3D conformal radiotherapy for non-small cell lung cancer: a preliminary report.

To study the intra-thoracic failure pattern, clinical target volume (CTV) and survival status following 3D conformal radiotherapy (3DCRT) boost for non-small cell lung cancer (NSCLC). From May 1994 through June 1998, 33 patients (26 male, seven female) with NSCLC were treated with a complete course of radiotherapy (RT) in our institute. Group A included 10 patients receiving radical operation and adjuvant postoperative RT. The other 23 patients (groups B and C) received definitive radiotherapy as local treatment. Among them there were seven cases as group B (stage I-II) and 16 cases as group C (stage III). Fifteen (15/33) patients received chemotherapy. The radiotherapy strategy constituted conventional AP/PA radiotherapy (RT) 19.8-45 Gy (median 39.6 Gy) plus 3DCRT boost 6-34.2 Gy (median 20 Gy). The median total tumor dose was 59.6 Gy (ranging from 39.8 to 64.8 Gy). Patients were followed up regularly (6/33) or until their death (27/33). Nineteen patients received follow-up chest computed tomography (CT). The relationship between intra-thoracic failure found by chest CT and the initial RT and boost RT fields was analyzed. Local failure was defined as one of the following: clinical disease progression, CXR progression or relapse noted by CT. The overall survival (OS) and local failure free survival (LFF) were obtained using the Kaplan-Meier method. Sixteen intra-thoracic failures were noted in 15 follow-up chest CT examinations, which included nine in-field relapses, three partial in-field relapses and four out-field relapses. The 2-year OS and LFF for groups A, B and C were 78.8/59.2, 14.2/16.7 and 6.2/7.1% respectively. RTOG grade III/IV complications included one pneumothorax (RTOG grade III). Our retrospective study showed that selective omission of contralateral mediastinal lymph node station irradiation may be appropriate in RT for NSCLC. Chest wall and pleural relapses may not be a negligible cause of intra-thoracic failure after RT for NSCLC.

Curative radiotherapy for technically operable stage I nonsmall cell lung cancer

Purpose : Retrospective study of patients with Stage I nonsmall cell lung cancer (NSCLC) unable to undergo surgery or refusing surgery. Methods and Materials : Between 1984 and 1990, 47 patients with technically operable Stage I NSCLC received hypofractionated radiotherapy. The total dose varied from 32 Gy in six fractions (two fractions/week) or 40 Gy split course in ten fractions (low-dose schedules) to 48 Gy in 12 fractions or 56 Gy in 20 fractions (high-dose schedules). The mean age of the patients was 75 years. Three patients refused surgery and 44 patients were inoperable due to their medical condition. Severe associated disease was present in 34 patients (72.3%). Results : The intrathoracic recurrence rate was 25.5%. In a multivariate analysis, tumor size was identified as the only significant factor predictive for intrathoracic failure ( p < 0.001). Disease-specific survival was 90, 53, and 32% at 1, 3, and 5 years, respectively. In Cox's proportional hazards analysis, only tumor size was predictive for disease-specific survival. Overall survival (all causes) was 70, 33, and 15% at 1, 3, and 5 years, respectively. In Cox's proportional hazards analysis, only the presence of severe associated disease was predictive for overall survival ( p < 0.01), while tumor size did not attain statistical significance ( p = 0.08). There were no severe acute or late side-effects. Conclusion : Radiotherapy can effectively control small nonsmall cell tumors. The reported results are comparable to those achieved with more fractionated radiation schedules. In patients of advanced age or in poor medical condition, hypofractionated radiotherapy can be given with curative intent, with minimal burden to the patient.

Limited-stage small-cell lung cancer: patterns of intrathoracic recurrence and the implications for thoracic radiotherapy.

This analysis was performed to determine the most appropriate volume that should be encompassed by thoracic radiation treatments (TRTs) for patients with limited-stage small-cell lung cancer (LSSCLC) who have responded to initial chemotherapy. A retrospective review of all patients (N = 67) with LSSCLC who were not entered onto a research protocol and were treated at our institution between the years of 1982 and 1990 was performed. Fifty-nine of 67 patients had adequate information regarding the size of the tumor before the start of chemotherapy (computed tomographic [CT] scan of chest or chest x-ray), the size of the tumor before TRT, and the TRT field size based on a simulation radiography. All 59 patients were treated with cyclophosphamide-based chemotherapy, and TRT was generally delivered concomitantly with chemotherapy following two to three cycles of chemotherapy alone. Of 59 patients, 28 were treated with TRT field sizes that encompassed postchemotherapy tumor volumes, and 31 patients were treated with TRT field sizes that encompassed prechemotherapy tumor volumes (defined as a volume that included at least a 1.5-cm margin on the prechemotherapy tumor volume). Nineteen patients had an intrathoracic recurrence of disease as the first site of recurrent small-cell carcinoma: 10 of 31 patients treated with TRT fields that encompassed prechemotherapy tumor volumes and nine of 28 patients treated with TRT fields that encompassed postchemotherapy tumor volumes. For the 28 patients treated with TRT fields that encompassed postchemotherapy tumor volumes, the greatest distance that the prechemotherapy tumor volume (without margins) extended beyond the edge of the TRT field was 0.5 to 5.0 cm, with a median of 2.5 cm. All 19 of the intrathoracic recurrences were in-field failures, although two patients (one prechemotherapy volume and one postchemotherapy volume) did have concurrent pleural effusions. These results indicate that the use of TRT fields that encompass postchemotherapy tumor volumes does not increase the risk of marginal failures or intrathoracic failures outside the TRT field.

Local Failure in Patients Treated with Radiotherapy and Multidrug Chemotherapy for Small Cell Lung Cancer

Fifty-three patients with small cell carcinoma of the lung were treated with chemotherapy and radiotherapy, 40 Gy in the chest tumour. Intrathoracic failure occurred in 89% of the cases with extensive disease and in 60% of those with limited disease. Since 86% of all failures were localized within the target volume, one can conclude that in most cases the radiation dose was too low for eradication of the tumour. The treatment technique resulted in dose inhomogeneities of more than +/- 5% in 45% of the cases. The high local failure rate might indicate the need of improved radiotherapy, in the first place higher radiation dose. However, 82% of the patients with limited disease and local failure and 50% of those without local failure also developed distant metastases. This might indicate that the curative potential of improved thoracic radiotherapy probably is limited. Besides, lethal treatment toxicity affected particularly patients in whom local cure had been achieved, indicating the difficulty of increasing the treatment intensity without increasing the lethal toxicity in potentially curable cases.

Results of radical radiation therapy in clinical stage I, technically operable non-small cell lung cancer

From 1970 to 1983, 1,646 lung cancer patients were referred for treatment to the Hunter Radiation Therapy Center, Yale-New Haven Hospital. Forty-three patients had clinical Stage I non-small cell lung cancer felt to be surgically resectable but were treated with radical radiation therapy either for medical reasons (37 patients) or because the patient refused surgery (six patients). This group of clinical Stage I lung cancer patients is understaged by modern criteria since the majority of patients did not have thoracic CT scans and staging was based on fairly limited clinical and radiographic studies. The histological diagnosis was squamous cell carcinoma in 53% of the Stage I patients, adenocarcinoma in 25%, and other non-small cell histologies in 22%. All patients were treated with megavoltage irradiation and the mediastinum was treated in 88% of the patients. Eleven patients were treated with a continuous course (CC) and 32 patients received split course (SC) therapy based on physician preference. The CC consisted of a median fraction size of 200 cGy to a total median dose of 5900 cGy in 6–7 weeks. The SC used a median fraction site of 275 cGy to a total median dose of 5400 cGy over a 6-week period with a 2-week rest in the middle of treatment. The actuarial survival rate of the 43 clinical Stage I patients was 36% at 3 years and 21% at 5 years. Intrathoracic failures occurred in 39% of the patients. Despite the fact that the CC group was similar to the SC group in terms of age, histology, and tumor extent, the CC patients had a lower thoracic failure rate ( 2 11 ) versus 15 32 ), a longer median survival (51.6 months versus 27 months), and a better actuarial 5-year survival rate (45% versus 12%) when compared to the SC patients. Using Cox regression analysis to compare survival curves, the CC group had a significantly better survival compared to the SC group ( p = .04).

Impact of tumor control on survival in carcinoma of the lung treated with irradiation

The long-term results in tumor response, intrathoracic tumor control and survival are reported in patients with medically inoperable or unresectable non-oat cell and small cell carcinoma of the lung. In 376 patients with stages T1–3, NO-2 carcinoma of the lung tumors, accessioned to a Radiation Therapy Oncology Group (RTOG) randomized study to evaluate different doses of irradiation, a higher complete response rate (24%), intrathoracic tumor control (67%) and three year survival (15%) was observed with 6000 cGy, compared with lower doses of irradiation (4000 or 5000 cGy). Increased survival was noted in patients with complete tumor response. Three year survival in complete responders was 23%, in partial responders, 10%, and in patients with stable disease, 5%. Patients treated with 6000 cGy had an overall intrathoracic failure rate of 33% at 3 years, compared with 42% for those treated with 5000 cGy, 44% for patients receiving 4000 cGy with split course, and 52% for those treated with 4000 cGy continuous course ( p = 0.02). Patients surviving 6 or 12 months exhibited a statistically significant increased survival when the intrathoracic tumor was controlled. Patients treated with 5000–6000 cGy, showing tumor control, had a three year survival of 22%, versus 10%, if they had intrathoracic failure ( p = 0.05). In patients treated with 4000 cGy (split or continuous), the respective survival was 20% and 10%, if the intrathoracic tumor was controlled ( p = 0.001). In patients surviving 12 months after treatment with 5000–6000 cGy, on whom the intrathoracic tumor was controlled, the median survival was 23 months, in contrast to 12 months, if they developed intrathoracic failure ( p = 0.05). In patients treated with 4000 cGy, the median survival was 17 months with control and 12 months without control of the intrathoracic tumor. ( p = 0.008). In another RTOG study for patients with more advanced tumors (T4 or N3), those with local tumor control at 12 months had a three year survival rate of 25%, compared with 5% for those with thoracic failures. These differences are statistically significant ( p = 0.006). Higher doses of irradiation yield a greater proportion of complete response, higher intrathoracic tumor control and better survival in non-oat cell medically inoperable or unresectable carcinoma of the lung. In a randomized study, the Southeastern Cancer Study Group (SECSG) reported that patients with small cell carcinoma of the lung given thoracic irradiation (4000 cGy in split course) in addition to Cytoxan, Adriamycin, and Vincristine (CAV) for a minimum of 6 cycles plus brain irradiation (3600 cGy, 15 fractions split course) at two years, had a higher intrathoracic tumor control (65%) than patients not given thoracic irradiation (52%). However, at 3 to 4 years, the intrathoracic failure rate was 50% for the patients receiving thoracic irradiation (28% in-field and 17% recurrence outside the radiotherapy field), in contrast to 52% intrathoracic failure without thoracic irradiation. The 2 year survival in the patients receiving thoracic irradiation was 35%, compared to 20% for those not receiving thoracic irradiation. At 3 years, however, the survival is similar in both groups. Among those patients eligible for consolidation (minimum of 6 cycles of chemotherapy without progressive disease), the 3 year survival was 35% for the group receiving thoracic irradiation and 20% for those treated with chemotherapy and brain irradiation alone ( p = 0.04). In both treatment groups, the only long-term survivors were those patients who did not develop chest relapses or distant metastases. All patients who failed in the chest, with or without distant metastases, died within 36 months. Intrathoracic tumor control is clearly associated with improved survival in patients with small cell carcinoma of the lung.

Prognostic groups for management of localized Hodgkin's disease.

Two hundred fifty-two patients receiving radical irradiation for clinical stages I and II Hodgkin's disease between 1968 to 1977 had an actuarial ten-year survival rate of 78% and a relapse-free rate of 61%. Sixty-seven patients receiving chemotherapy followed by radiation had a 78% survival rate and a 63% relapse-free rate. Independent prognostic factors for survival and relapse were age, stage, and histology. Disease bulk was predictive only of relapse. Neither site of presentation above or below the diaphragm nor presence of mediastinal involvement was predictive for survival or relapse; however, patients with large mediastinal masses (greater than or equal to 10 cm absolute diameter) had a significantly higher intrathoracic failure rate with conventional mantle irradiation. Analysis of failure, according to age, clinical stage, and histologic type, showed three groups of patients defined according to the risk of relapse with radiation therapy: those with isolated upper cervical stage IA disease (group 1, relapse rate 8%), younger patients with localized stages I and II disease of favorable histologic type (group 2, relapse rate 35%), and older patients with extensive or symptomatic stages I and II disease of less favorable histologic type (group 3, relapse rate 70%). Subsequent analysis of radiation treatment volume indicates that the use of upper abdominal irradiation for patients in group No. 2 could yield results equivalent to those achieved with radiation therapy for surgically staged patients.