A Study to Evaluate Chemotherapy Combined with Immune Checkpoint Inhibitor for Operable Stage IIIA/B Non-Small Cell Lung C

Overview

About this study

The purpose of this study is to increase N2 nodal clearance (N2NC) to 50% or greater for combined platinum doublet chemotherapy with durvalumab induction therapy from historical rate of 30% for platinum doublet chemotherapy alone in patients with potentially resectable stage IIIA/B (N2) NSCLC.

 

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

Operability Criteria:

1. ECOG Performance Status 0-1.

2. Absence of major associated comorbidities that increase the surgery risk to an
unacceptable level.

3. Pulmonary function capacity capable of tolerating the proposed lung resection. FEV1 at
least 2 L. If less than 2 L, the predicted postoperative forced expiratory volume in 1
second (FEV1) must be >0.8 L or be >35% of the predicted value. Postoperative
predicted DLCO ≥35% is required.

Inclusion Criteria:

1. Patients who are at least 18 years of age.

2. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.

3. Life expectancy of at least 12 weeks.

4. Patients with potentially resectable IIIA/B (T1-3, N2) NSCLC (per the 8th
International Association for the Study of Lung Cancer classification) who are
candidates for surgery with intent of R0 resection. Invasive T3 disease (eg, phrenic
nerve, pericardium, chest wall other than Pancoast superior sulcus) may be included if
the surgeon and study team deem it to be resectable. T4 disease per AJCC 8th edition
staging system is excluded given the lack of benefit of surgery in T4N2.

5. Patients must be evaluated by a thoracic surgeon within 4 weeks of registration.

6. Operability is defined as having adequate pulmonary, cardiac, renal, nutritional,
musculoskeletal, neurologic, and cognitive capacity to undergo major pulmonary
resection with acceptable morbidity and mortality.

7. N2 nodes must be discrete (ie, not invading surrounding structures) and less than 3 cm
in maximum diameter.

8. Measurable disease according to Response Evaluation Criteria in Solid Tumors version
1.1 (RECIST v1.1).

9. Pathologically proven N2 disease within 4 weeks of registration. PET/CT positivity in
the ipsilateral mediastinal nodes will not be sufficient to establish N2 nodal status.
Mediastinal lymph node sampling biopsy is required pre-operatively by at least one of
the following:

- Endobronchial Ultrasound Transbronchial Needle Aspiration (EBUS-TBNA);

- Mediastinoscopy;

- Mediastinotomy (Chamberlain procedure);

- Endoscopic ultrasound guided node aspiration (EUS);

- Video-assisted thoracoscopy; OR

- Fine needle aspiration by image guidance.

- Endobronchial ultrasound (EBUS) or mediastinoscopy or other tissue sampling (at
least 2 stations must be biopsied, with at least one station positive for N2
disease). If there are any mediastinal nodes suspicious by CT (>1.5 cm) or PET in
N3 stations, they must be biopsied. If biopsy proven involvement in an N3
station, the patient is excluded.

10. Mediastinal nodal biopsy or aspiration can only be omitted in the special circumstance
in which ALL of the following are true:

- The tumor is left sided;

- The only mediastinal nodal involvement is a node visible in the AP (level 5)
region on CT scan;

- Distinct primary tumor separate from the nodes; AND

- Biopsy proven non-small cell histology from the primary tumor.

11. No prior history of thoracic radiation.

12. Organ and marrow function definitions (example below)

- leukocytes ≥3,000/mcL

- absolute neutrophil count ≥1,500/mcL

- platelets ≥100,000/mcL

- Hemoglobin >9.0 g/dL

- total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

- creatinine within normal institutional limits OR

- creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels
above institutional normal.

13. Patients are capable of giving informed consent and/or have an acceptable surrogate
capable of giving consent on the subject's behalf.

14. Nonpregnant and non-nursing. The effect of durvalumab on the fetus is unknown.

15. Women of childbearing potential (WOCBP) must be willing to use 2 methods of birth
control or be surgically sterile, or abstain from heterosexual activity for the course
of the study through 3 months after the last dose of study medication. Patients of
childbearing potential are those who have not been surgically sterilized or have not
been free of menses >1 year.

16. Evidence of postmenopausal status or negative urinary or serum pregnancy test for
female premenopausal patients. Women will be considered postmenopausal if they have
been amenorrheic for 12 months without an alternative medical cause. The following
age-specific requirements apply:

- Women <50 years of age would be considered postmenopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and if they have luteinizing hormone and follicle-stimulating hormone
levels in the postmenopausal range for the institution or underwent surgical
sterilization (bilateral oophorectomy or hysterectomy).

- Women ≥50 years of age would be considered postmenopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation-induced menopause with last menses >1 year ago, had
chemotherapy-induced menopause with last menses >1 year ago, or underwent
surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or
hysterectomy).

17. Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up.

18. Male patients must agree to use an adequate method of contraception starting with the
first dose of study therapy through 12 weeks after the last dose of study therapy.

Exclusion Criteria:

1. Any prior treatment for NSCLC.

2. Prior thoracic radiation.

3. Patients with ≥Grade 2 peripheral neuropathy.

4. Any active or history of autoimmune disease (including any history of inflammatory
bowel disease) or history of a syndrome that required systemic steroids or
immunosuppressive medications, except for patients with vitiligo or resolved childhood
asthma/atopy.

5. Patients requiring systemic treatment with either corticosteroids (>10 mg daily
prednisone equivalents) or other immunosuppressive medications within 14 days of study
drug administration. Inhaled or topical steroids and adrenal replacement doses <10 mg
daily prednisone equivalents are permitted in the absence of active autoimmune
disease.

6. Patients with previous malignancies (except nonmelanoma skin cancers, in situ bladder,
gastric, breast, colon or cervical cancers/dysplasia) are excluded unless a complete
remission was achieved at least 2 years prior to study entry and no additional therapy
is required or anticipated to be required during the study period.

7. History of solid organ transplant.

8. N3 nodal disease.

9. Mixed small cell/NSCLC will be excluded.

10. Pregnant or breastfeeding.

11. History of allogenic organ transplantation.

12. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg, colitis or Crohn's disease], active diverticulitis
with the exception of diverticulosis, systemic lupus erythematosus, Sarcoidosis
syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease,
rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to
this criterion:

- Patients with vitiligo or alopecia.

- Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone
replacement.

- Any chronic skin condition that does not require systemic therapy.

- Patients without active disease in the last 5 years may be included but only
after consultation with the study physician.

- Patients with celiac disease controlled by diet alone.

13. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
situations that would limit compliance with study requirement, substantially increase
risk of incurring AEs or compromise the ability of the patient to give written
informed consent.

14. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms
calculated.

Eligibility last updated 6/13/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Shanda Blackmon, M.D., M.P.H.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

  • First-line therapy for advanced non-small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone in a phase 2 trial. Read More on PubMed
  • Antibodies that block programmed death 1 (PD-1) protein improve survival in patients with advanced non-small-cell lung cancer (NSCLC) but have not been tested in resectable NSCLC, a condition in which little progress has been made during the past decade. Read More on PubMed
  • Most patients with locally advanced, unresectable, non-small-cell lung cancer (NSCLC) have disease progression despite definitive chemoradiotherapy (chemotherapy plus concurrent radiation therapy). This phase 3 study compared the anti-programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC who did not have disease progression after two or more cycles of platinum-based chemoradiotherapy. Read More on PubMed
  • Multimodality therapy has curative potential in locally advanced NSCLC. Mediastinal nodal sterilization (MNS) after induction chemoradiotherapy (CRT) can serve as an intermediate marker for efficacy. NRG Oncology Radiation Therapy Oncology Group (RTOG) 0229 demonstrated the feasibility and efficacy of combining full-dose radiation (61.2 Gy) with chemotherapy followed by resection and chemotherapy. On the basis of that experience and evidence that EGFR antibodies are radiosensitizing, we explored adding panitumumab to CRT followed by resection and consolidation chemotherapy in locally advanced NSCLC with a primary end point of MNS. Read More on PubMed
  • Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1). Read More on PubMed
  • The role of postoperative radiotherapy (PORT) in the treatment of patients with completely resected non-small cell lung cancer (NSCLC) was not clear. A systematic review and individual participant data meta-analysis was undertaken to evaluate available evidence from randomised controlled trials (RCTs). These results were first published in Lung Cancer in 2013. Read More on PubMed
  • Induction therapy is often recommended for patients with clinical stage IIIA-N2 (cIIIA/pN2) lung cancer. We examined whether postinduction positron emission tomography (PET) scans were associated with ypN2 disease and survival of patients with cIIIA/pN2 disease. Read More on PubMed
  • The IASLC Staging and Prognostic Factors Committee has collected a new database of 94,708 cases donated from 35 sources in 16 countries around the globe. This has now been analysed by our statistical partners at Cancer Research And Biostatistics and, in close collaboration with the members of the committee proposals have been developed for the T, N, and M categories of the 8th edition of the TNM Classification for lung cancer due to be published late 2016. In this publication we describe the methods used to evaluate the resultant Stage groupings and the proposals put forward for the 8th edition. Read More on PubMed
  • The objective of this study was to compare survival in patients with stage IIIA (N2) non-small-cell lung cancer (NSCLC) treated with definitive chemoradiation (CRT) or surgery plus neoadjuvant chemoradiation or chemotherapy (CRTS). Read More on PubMed
  • One of the standard options in the treatment of stage IIIA/N2 non-small-cell lung cancer is neoadjuvant chemotherapy and surgery. We did a randomised trial to investigate whether the addition of neoadjuvant radiotherapy improves outcomes. Read More on PubMed
  • Accurate preoperative staging and restaging of mediastinal lymph nodes in patients with potentially resectable non-small-cell lung cancer (NSCLC) is of paramount importance. In 2007, the European Society of Thoracic Surgeons (ESTS) published an algorithm on preoperative mediastinal staging integrating imaging, endoscopic and surgical techniques. In 2009, the International Association for the Study of Lung Cancer (IASLC) introduced a new lymph node map. Some changes in this map have an important impact on mediastinal staging. Moreover, more evidence of the different mediastinal staging technique has become available. Therefore, a revision of the ESTS guidelines was needed. In case of computed tomography (CT)-enlarged or positron emission tomography (PET)-positive mediastinal lymph nodes, tissue confirmation is indicated. Endosonography [endobronchial ultrasonography (EBUS)/esophageal ultrasonography (EUS)] with fine-needle aspiration (FNA) is the first choice (when available), since it is minimally invasive and has a high sensitivity to rule in mediastinal nodal disease. If negative, surgical staging with nodal dissection or biopsy is indicated. Video-assisted mediastinoscopy is preferred to mediastinoscopy. The combined use of endoscopic staging and surgical staging results in the highest accuracy. When there are no enlarged lymph nodes on CT and when there is no uptake in lymph nodes on PET or PET-CT, direct surgical resection with systematic nodal dissection is indicated for tumours ≤ 3 cm located in the outer third of the lung. In central tumours or N1 nodes, preoperative mediastinal staging is indicated. The choice between endoscopic staging with EBUS/EUS and FNA or video-assisted mediastinoscopy depends on local expertise to adhere to minimal requirements for staging. For tumours >3 cm, preoperative mediastinal staging is advised, mainly in adenocarcinoma with high standardized uptake value. For restaging, invasive techniques providing histological information are advisable. Both endoscopic techniques and surgical procedures are available, but their negative predictive value is lower compared with the results obtained in baseline staging. An integrated strategy using endoscopic staging techniques to prove mediastinal nodal disease and mediastinoscopy to assess nodal response after induction therapy needs further study. Read More on PubMed
  • Sifalimumab is a fully human immunoglobulin G1κ monoclonal antibody that binds to and neutralizes a majority of the subtypes of human interferon-α. Sifalimumab is being evaluated as a treatment for systemic lupus erythematosus (SLE). The primary objectives of this analysis were (a) to develop a population pharmacokinetic model for sifalimumab in SLE; (b) to identify and quantitate the impact of patient/disease characteristics on pharmacokinetic variability; and (c) to evaluate fixed versus body weight (WT)-based dosing regimens. Read More on PubMed
  • To evaluate mediastinal nodal clearance (MNC) rates after induction chemotherapy and concurrent, full-dose radiation therapy (RT) in a phase II trimodality trial (Radiation Therapy Oncology Group protocol 0229). Read More on PubMed
  • Therapeutic biologics are often administered based on body size. A previous study has found that fixed dosing performs similarly to body size-based dosing in reducing intersubject variability in drug exposure across the mAbs studied. This study extended this evaluation to other therapeutic proteins and peptides. Eighteen therapeutic proteins and peptides with published population pharmacokinetic (PK) and/or pharmacodynamic (PD) models were selected for dosing approach evaluation. The relationships between body size and drug exposure (and PD end point when available) were evaluated, and simulation studies were conducted to compare the performance of the 2 dosing approaches. The results showed that fixed dosing performed better for 12 of 18 selected biologics in terms of reducing intersubject variability in exposure at both population and individual levels, whereas body size-based dosing performed better for the other 6 molecules. This result is consistent with the findings for mAbs. Therefore, fixed dosing is recommended for first-in-human studies of proteins and peptides along with mAbs. The final dosing approach for phase 3 studies should be determined based on a full assessment of body size effect on PK/PD when data are available and the therapeutic window of the drug. Read More on PubMed
  • To review the dose limits and standardize the three-dimenional (3D) radiographic definition for the organs at risk (OARs) for thoracic radiotherapy (RT), including the lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. Read More on PubMed
  • To compare preoperative chemotherapy (ChT) and preoperative chemoradiotherapy (ChT-RT) in operable Stage III non-small-cell lung cancer. Read More on PubMed
  • Although without clear scientific rationale, body size-based dosing is often used for administering monoclonal antibodies (mAbs). This simulation study compared the performance of body size-based and fixed dosing in reducing pharmacokinetic (PK) and/or pharmacodynamic (PD) variability in adults for 12 mAbs with published population PK and/or PD models. At the population level, 95th percentile intervals of concentration-time profiles, distribution, and variability of exposure for 1000 subjects after both dosing approaches were examined. At the individual level, the difference between the exposures of patients with extreme body sizes from the typical exposure following both approaches was compared. The results show that the 2 dosing approaches perform similarly across the mAbs investigated with fixed dosing being better for some mAbs and body size-based dosing being better for the others. Based on this finding, we recommend using fixed dosing in first-in-human (FIH) adult studies because it offers other advantages. When sufficient data become available, a full assessment of body size effect on PK/PD should be conducted to determine the optimal dosing approach for phase 3 trials. Other factors that may affect the selection of dosing approach were also discussed. Dosing approach for mAbs in the pediatric population is out of the scope of this study. Read More on PubMed
  • Results from phase II studies in patients with stage IIIA non-small-cell lung cancer with ipsilateral mediastinal nodal metastases (N2) have shown the feasibility of resection after concurrent chemotherapy and radiotherapy with promising rates of survival. We therefore did this phase III trial to compare concurrent chemotherapy and radiotherapy followed by resection with standard concurrent chemotherapy and definitive radiotherapy without resection. Read More on PubMed
  • Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation studies and literature reviews. HIGHLIGHTS OF REVISED RECIST 1.1: Major changes include: Number of lesions to be assessed: based on evidence from numerous trial databases merged into a data warehouse for analysis purposes, the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total (and from five to two per organ, maximum). Assessment of pathological lymph nodes is now incorporated: nodes with a short axis of 15 mm are considered measurable and assessable as target lesions. The short axis measurement should be included in the sum of lesions in calculation of tumour response. Nodes that shrink to <10mm short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer required in randomised studies since the control arm serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5mm absolute increase is now required as well to guard against over calling PD when the total sum is very small. Furthermore, there is guidance offered on what constitutes 'unequivocal progression' of non-measurable/non-target disease, a source of confusion in the original RECIST guideline. Finally, a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included. Imaging guidance: the revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions. Read More on PubMed
  • Preoperative chemotherapy improves survival in patients with stage III non-small-cell lung cancer (NSCLC) amenable to resection. We aimed to assess the additional effect of preoperative chemoradiation on tumour resection, pathological response, and survival in these patients. Read More on PubMed
  • To update eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone. Read More on PubMed
  • Induction chemotherapy before surgical resection increases survival compared with surgical resection alone in patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC). We hypothesized that, following a response to induction chemotherapy, surgical resection would be superior to thoracic radiotherapy as locoregional therapy. Read More on PubMed
  • CALGB 8935 was a phase II protocol for mediastinoscopically staged IIIA (N2) non-small cell lung cancer. Induction cisplatin/vinblastine chemotherapy was followed by surgical resection, adjuvant cisplatin/vinblastine, and radiotherapy. We now evaluate the prognosis of pathologic nodes. Read More on PubMed
  • To update the 2000 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSF). Read More on PubMed
  • Our objectives were to develop the population pharmacokinetic (PK) for pertuzumab and examine the variability of steady-state trough serum concentrations (C(SS,trough)) and exposure after fixed, body-weight-based, or body-surface area (BSA)-based dosing methods in cancer patients. Read More on PubMed
  • Accurate delineation of the mediastinal and hilar lymph node regions is essential for a reproducible definition of target volumes used in conformal irradiation of non-small-cell lung cancer. The goal of this work was to generate a consensus to delineate these nodal regions based on definitions from the American Joint Committee on Cancer. Read More on PubMed
  • A multicenter, phase II trial investigated the efficacy and toxicity of neoadjuvant docetaxel-cisplatin in locally advanced non-small-cell lung cancer (NSCLC) and examined prognostic factors for patients not benefiting from surgery. Read More on PubMed
  • Prostate-specific antigen (PSA) is a glycoprotein that is found almost exclusively in normal and neoplastic prostate cells. For patients with metastatic disease, changes in PSA will often antedate changes in bone scan. Furthermore, many but not all investigators have observed an association between a decline in PSA levels of 50% or greater and survival. Since the majority of phase II clinical trials for patients with androgen-independent prostate cancer (AIPC) have used PSA as a marker, we believed it was important for investigators to agree on definitions and values for a minimum set of parameters for eligibility and PSA declines and to develop a common approach to outcome analysis and reporting. We held a consensus conference with 26 leading investigators in the field of AIPC to define these parameters. Read More on PubMed
  • Postoperative radiotherapy is commonly used to treat patients with completely resected nonsmall cell lung carcinoma, but its effect on overall survival has not been established. Read More on PubMed
  • The role of postoperative radiotherapy in treatment of patients with completely resected non-small-cell lung cancer (NSCLC) remains unclear. We undertook a systematic review and meta-analysis of the available evidence from randomised trials. Read More on PubMed
  • The role of post-operative radiotherapy for patients with non-small-cell lung cancer (NSCLC) is unclear despite five previous randomised trials. One deficiency with these trials was that they did not include adequate TNM staging, and so the present randomised trial was designed to compare surgery alone (S) with surgery plus post-operative radiotherapy (SR) in patients with pathologically staged T1-2, N1-2. M0 NSCLC. Between July 1986 and October 1993, 308 patients (154 S, 154 SR) were entered from 16 centres in the UK. The median age of the patients was 62 years, 74% were male, > 85% had normal or near normal levels of general condition, activity and breathlessness, 68% had squamous carcinoma, 52% had had a pneumonectomy, 63% had N1 disease and 37% N2 disease. SR patients received 40 Gy in 15 fractions starting 4-6 weeks post-operatively. Overall there was no advantage to either group in terms of survival, although definite local recurrence and bony metastases appeared less frequently and later in the SR group. In a subgroup analysis, in the N1 group no differences between the treatment groups were seen, but in the N2 group SR patients appeared to gain a one month survival advantage, delayed time to local recurrence and time to appearance of the bone metastases. There is, therefore, no clear indication for post-operative radiotherapy in N1 disease, but the question remains unresolved in N2 disease. Read More on PubMed
  • In the period 1988-1992, 74 consecutive radically resected patients with NSCLC were randomised to postoperative radiotherapy or surgery alone in order to evaluate the influence of postoperative radiotherapy on survival. There were 61 males and 13 females, aged 35-80 years, median 59 years. Their distribution by stage was as follows: pT1N2 = 19, pT2N2 = 54, pT3N2 = one patient; histology: 32 squamous, 32 adeno and 10 large cell carcinomas; surgery: atypical resection in six, lobectomy in 27, bilobectomy in ten, and pneumonectomy in 31 patients. In 27 patients, only one lymph node in a single mediastinal lymph node site was affected; in 31 patients more than one lymph node in one site; in 16 patients more sites were affected. In 35/74 patients radiotherapy of hilar and mediastinal sites with 3000 cGy in 2 weeks was performed. On December 31, 1994, 19 patients (26%) were still alive; 39/55 patients died of the following causes: locoregional failure-10(26%), distant metastases- 25 (64%), other tumor-unrelated causes-four patients (10%). Five-year survival rates did not show statistically significant differences between the irradiated and surgically treated patients only with respect to sex, pTNM stage, histology and frequency of locoregional failure. The number of metastatic mediastinal lymph nodes was the only significant prognostic factor (P < 0.005) in both randomised groups. Read More on PubMed
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