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Philip Bonomi
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MS 11 - Combined Modality Treatment for Superior Sulcus Tumors (ID 533)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Locally Advanced NSCLC
- Presentations: 5
- Moderators:G.D. Castro, Philip Bonomi
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 503
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MS 11.01 - Preoperative Chemoradiotherapy Followed by Surgical Resection (ID 7694)
11:00 - 11:15 | Presenting Author(s): Hideo Kunitoh
- Abstract
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Superior sulcus tumors (SSTs), involving structures at the thoracic inlet, have posed a challenging problem for surgeons, radiation oncologists and medical oncologists alike, ever since they were first described[1)]. Pre-operative radiotherapy had long been the community standard in the management of SSTs. However, both the complete resection rate (approximately 50%) and long-term survival (approximately 30%) rate had remained poor and unchanged over 40 years, since the first treatment strategy was reported in the 1960’s. Local control had remained the main problem, adversely affecting the quality of life as well as the survival of the patients[2)]. Encouraged by the promising data of concurrent chemoradiotherapy for mediastinal node-positive N2 NSCLC, two prospective studies applied this modality as preoperative therapy for patients with SSTs; one from the US (led by the Southwest Oncology Group SWOG9416-Intergroup Trial 0160[3)]), and the other from Japan (by the Japan Clinical Oncology Group, JCOG 9806[4)]). In both trials, patients with SSTs received two cycles of cisplain-based chemotherapy (etoposide-cisplatin in US, mitomycin-vindesine-cisplatin in Japan), concurrently given with thoracic radiotherapy 45Gy/27fr. Then they underwent surgical resection. Boost radiotherapy was given to unresected/imcompletely resected tumors. In spite of minor differences, the results of the two trials were strikingly similar (Table). The intensive trimodality approach was found to be feasible in both reports, with a reasonably low toxic death rate of 4%. The resection rate, which had remained unchanged at about 50% for almost 40 years with conventional preoperative radiotherapy, was approximately 70% in both studies. Particularly noteworthy was the reproducibility of the favorable survival data, with a 5-year OS of 44% in the US trial and 56% in the Japanese trial, which were clearly superior to the historical value of 30%. Although T factor (T3 vs. T4) was not a significant prognostic factor in the US trial, T3 patients did far better than T4 in the Japanese study (Figure), reflecting lower resection rate (78% vs. 40%).Figure 1 A shift in the trend of clinical problems also became clear. The relapse patterns changed from predominantly locoregional to mainly distant recurrences in cases with complete resection, and a significant number of such patients suffered from metastasis in the brain as the initial site of relapse. In the JCOG study, 7-year follow-up data[5)] revealed that 21 (41%) of the 51 patients who underwent R0 resection relapsed; initial site of relapse included locoregional only in 1, distant metastasis only in 14 (5 were “brain only”), and both in 6. In contrast, out of the 24 patients who failed to get R0 resection, 18 got tumor recurrence, with 13 locoregional relapses. In order to improve the outcome, SWOG subsequently launched another trial, S0220, with docetaxel consolidation after the induction therapy[6)]. However, the overall survival was no better than the initial two reports, with the 3-year OS of 61%. The relapse pattern remained predominantly distant. Preoperative chemoradiotherapy was compared to conventional pre-operative radiotherapy in the Massachusetts General Hospital. In their retrospective analysis, Wright et al[7)] did show that pre-op chemoradiotherapy was better that pre-op radiotherapy, with 4-year OS of 84% vs. 49%. In their single-institute trial (#92-038) at the MD Anderson Cancer Center, Gomez et al reported[8)] the results of initial surgery followed by chemoradiotherapy in “resectable” SST. The result was comparable with those of the multi-institutional studies (Table), which included many “marginally resectable” tumors. Given the potential selection biases, the evidence would favor pre-operative chemoradiotherapy strategy.
In summary, preoperative chemoradiotherapy is the current standard of care for patients with SSTs. Several critical questions remain unsolved, however, including effective suppression of micrometastases in cases with R0 resection, prevention of brain metastases, and management of N2 SSTs, which were excluded from the hitherto reported trials. References 1) N Engl J Med 337: 1370-1376, 1997 2) J Thorac Cardiovasc Surg 119: 1147-1153, 2000 3) J Clin Oncol 25: 313-318, 2007 4) J Clin Oncol 26: 644-649, 2007 5) Proc Am Soc Clin Oncol 28 suppl: 2010, (abstr 7025) 6) Ann Thorac Surg. 98: 402–410, 2014 7) Ann Thorac Surg 73:1541-4, 2002 8) Cancer 118: 444-51, 2012Trial JCOG9806 SWOG9416 MDA92-028 Patient accrual 76/ 3.6 years 116/ 4.3 years 32/ 13 years No. institutions 19 NR (5 groups) 1 Chemotherapy Pre-op Pre- & post-op Post-op Chemotherapy MVP EP EP Radiotherapy Pre-op Pre-op Post-op Radiotherapy 45Gy/25fr 45Gy/25fr 60Gy/50fr %T4 disease 26% 29% 22% (pathological) Radiological ORR 61% 42% N/A Resection rate 75% 80% 100% Complete resection rate 68% 76% 72% Pathological CR rate 16% 29% N/A Toxic death rate 4% 4.5% 0 OS at 3-years 62% NR NR OS at 5-years 56% 44% 50% OS at 7-years 52% 41% 50%
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MS 11.02 - Problems in the Management of Superior Sulcus Tumor (ID 7695)
11:15 - 11:30 | Presenting Author(s): Georgios Stamatis
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Pancoast tumors or superior pulmonary sulcus tumors (SSTs) are a rare subgroup of non-small cell lung carcinomas and occur in about 3-5% in patients with lung cancer. It is one of the most challenging thoracic malignancy to treat because of their proximity to vital structure in the thoracic inlet. In the last two decades improvements in appropriate preoperative staging, in multimodality treatment and development of new operative techniques have resulted in more curative treatment and better long-term results. However, in the preoperative assessment the role of positron emission tomography (PET) and magnetic resonance imaging (MRI) has not been studied specifically in SSTs, also imaging methods to access pathological response after induction treatment is not clearly defined. Furthermore, management of STSs with invasion of spine or subclavian vessels remains controversial. Invasion of these structures was traditionally considered as a contraindication to surgery because of technical difficulties and poor long-term results. Also, patients with SST and N2 or N3 disease had an extremely poor prognosis due to loco regional recurrences, so that due to previous recommendations, this group of patients should not be treated surgically except in a protocol setting. The surgical approach (anterior/posterior/combined) varies dependent on tumor spread and although lobectomy is recommended as the standard type of pulmonary resection, many authors reported no significant different survival rates after sublobar operations. Finally, brain metastases remain the most common form of distant relapse, the use of prophylactic cranial irradiation is not generally accepted. Clinical diagnosis and appropriate staging has to be conducted. SSTs are well accessible by transthoracic fine-needle aspiration. MRI is the modality of choice for imaging structures of the thoracic inlet, including the brachial plexus, subclavian vessels, spine and neural foramina. It shows local extent of the disease and is important for preoperative planning. EBUS-TBNA and PET is recommended for evaluation of mediastinal disease and distant metastasis before starting the induction treatment, mediastinoscopy is indicated to access pathological nodal response before surgery. A prospective phase II trial (SWOG INT 0160) showed that induction treatment with preoperative two cycles chemotherapy and concurrent radiotherapy with 45 Gy followed by surgery resulted in better tumor response and local control, higher rates of R0 resections and improved long-term overall survival, by low perioperative morbidity and mortality. Today, induction chemo radiotherapy followed by surgery has been established as standard treatment regimen for SSTs. Although vertebral body invasion and subclavian artery involvement are declared as negative prognostic factors, improvement in surgical techniques and cooperation of different surgical specialists, resulted in promising results for these difficult group of patients. Several authors described surgical techniques for tumor resection involving the transverse process only, or the intervertebral foramina, requiring hemivertebrectomies with spinal fixation, or the vertebral body, requiring total vertebral body resection with spinal fixation. In highly selected patients these extensive resections could be performed with acceptable morbidity and mortality in specialized centers with interdisciplinary teams of thoracic and spine surgeons. The en bloc resection technique provided acceptable recurrent rate (local 15%, distant 45%) and good long-term survival (25%-30% at 5-years). The introduction of the anterior approach made the resection of SSTs with subclavian artery involvement easier. After resection, the subclavian artery was reconstructed either with a ring supported polytetrafluoroethylene (PTFE) graft or direct by end-to-end anastomosis. Some authors reported about resection along the subadventitial plane to obtain tumor free margins or the use of autologous grafting. Five-year survival rates range between 25% and 32%. Extrapolating from the favorable results in other lung cancers, investigators have also considered induction chemoradiation for SSTs with mediastinal lymph node involvement (N2 disease), a group of patients previously considered hopeless. It is noteworthy that in two studies, no difference in median and overall survival was found between positive or negative pretreatment mediastinal N2 disease. Although these data should be interpreted with caution because they are liable to selection, they show that surgery is feasible with an acceptable outcome. Another important issue is that some authors found that ipsilateral supraclavicular lymph node is a local lymph node, so that patients with SSTs and N3 status (ipsilateral supraclavicular node involvement) showed a better prognosis than patients with N2 status (ipsilateral mediastinal node involvement). This have been confirmed in two larges and a few small series and underlines that ipsilateral supraclavicular N3 involvement could represent only local extension and may have a prognostic importance near to that of N1 disease. The influence of the type of lung resection, lobectomy versus sublobar resection, on the survival rates remains controversial. Lobectomy was associated with better survival compared with patients with wedge resections, but these data came predominantly from the pre-induction era with trimodality treatment. One important question is the necessity of lobectomy in patients with SSTs and pathological complete response (pCR). Some authors reported no significant different survival rates after sublobar operations in pCR patients and a higher incidence of wedge resection was found using the anterior approach only. Infiltration of the thoracic inlet increases the technical complexity of surgery, requiring extended resections and demanding reconstructive procedures. Completeness of resection represents one of the main factors influencing the long- term outcome of patients, pointed out in all publications about SSTs. Brain metastases remain one of the most common forms of relapse, prophylactic cranial irradiation (PCI) may be useful addition to preoperative chemoradiotherapy. Improvements in the combined preoperative treatment and surgical approach have significantly influenced local control and survival rates of SSTs. Further refinement of these techniques, also the addition of other chemotherapy agents or biologic agents as angiogenetic inhibitors or tyrosine kinase inhibitors could give some new perspectives in the treatment of SSTs. Further studies are needed to examine the effect of PCI on the survival after relapses in the brain. I declare no conflicts of interest.
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MS 11.03 - Surgical Approaches in Superior Sulcus Tumor (ID 7696)
11:30 - 11:45 | Presenting Author(s): Elie Fadel
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Complete en bloc resection is the corner stone of the treatment of solid tumors. Those located in the superior sulcus (SS) or thoracic inlet are known to have bad reputation because their resection represents a real technical challenge. The complexity of such surgery is due to the congestion of a very tight space (SS) by major neurovascular structures as well as to the proximity of the esophagus, the trachea and the spine. The preoperative work-up, in order to assess the involvement of such structures by SS tumors, may include, further to the routine bronchoscopy and cervico thoracic CT scan, an MRI to rule out spinal extension, venous angiography, subclavian arteriography or esophagoscopy. Many surgical approaches to remove SS tumors and many anatomical classifications have been reported during the last 6 decades. The goal of the surgical approach is to allow a wide and safe exposure of the SS, complete en-bloc resection of the tumor and all the involved structures and a potential arterial or spinal resection and reconstruction. The main goal of an anatomical classification is to facilitate the choice of the most appropriate surgical approach according to the extension of the tumor. After an anatomical description of the SS, we will review all the surgical approaches described in the literature to remove benign or malignant tumors developed in the SS. The emergence of new surgical techniques during the last 2 decades, such video-assisted and robotics surgeries had modify the surgical approaches in thoracic surgery. We will describe all the surgical approaches currently available to resect SS tumors with their advantages and their limits. Based on our experience we will describe a simplified anatomical classification of SS tumors. After identification of all contra-indications to SS tumor resection, we will describe the surgical approaches we use currently allowing when needed arterial and spinal resections and reconstructions.
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MS 11.04 - Radiation Therapy for Superior Sulcus Tumor (ID 8121)
11:45 - 12:00 | Presenting Author(s): Suresh Senan
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In 2003, an IASLC Consensus Report recommended that ‘superior sulcus tumors (Pancoast tumors, T3 or T4) should preferentially undergo trimodality treatment, including chemoradiation and surgery’ [Eberhardt WE, Lung Cancer 2003]. This recommendation was based on the early results of the phase II Intergroup Trial 0160) trial, findings which have been subsequently updated [Rusch VW, J Clin Oncol 2007]. Results of two other prospective phase II trials, namely the JCOG 9806 and the SWOG-Intergroup Trial S0220, support the use of the trimodality approach in superior sulcus tumors [Kunitoh H, J Clin Oncol 2008; Kernstine KH, Ann Thorac Surg 2014]. Between 30-40% of patients with a locally-advanced NSCLC can develop local disease recurrence following full-dose chemoradiation [Baker S, Radiat Oncol 2016]. As the impact of a local recurrence for patients with superior sulcus tumors can be great, the role of surgery remains relevant for this site. Recent ESMO guidelines have identified this patient subgroup as having an increased risk of an incomplete resection [Eberhardt WE, Ann Oncol 2015], and consequently, the role of concurrent CT-RT as an induction scheme is considered standard at centers with the available surgical expertise. This overview will address radiation-related topics such as dose and fractionation schemes, treatment fields, newer radiation delivery techniques (MRI-guided radiotherapy, protons), salvage radiotherapy for small volume recurrences, and the treatment of second primary lung tumors.
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MS 11.05 - Definitive Chemoradiotherapy in Superior Sulcus Tumor (ID 7697)
12:00 - 12:15 | Presenting Author(s): Everett E Vokes
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Superior sulcus tumors have been long defined as a distinct clinical entity. Symptoms including Horner’s syndrome and other neurologic findings as well as severe shoulder pain and SVC syndrome characterize this disease. Early on, the use of preoperative therapy was recognized as potentially useful. Over time, initial chemoradiotherapy followed by surgery has emerged as standard of care for patients with T3 or T4 lesions and N0 or N1 disease. 3-year survival rates of approximately 60% have been reported for surgically resectable patients with advanced disease. More recently, the addition of consolidation chemotherapy following subsequent surgery was evaluated, but its exact contributions to increasing survival remain unclear. The majority of patients will progress, usually with systemic disease and a large fraction of patients develop brain metastases. Patients with unresectable disease receive concurrent chemoradiotherapy as definitive therapy. Here, commonly used regimens such as the combination of cisplatin/etoposide, carboplatin/paclitaxel, and cisplatin/pemetrexed are utilized. However, more effective therapies are needed and special emphasis on increasing the systemic antitumor activity against micrometastatic disease will be required. The use of targeted therapies such as erlotinib or crizotinib for EGFR mutated or ALK fusion-related adenocarcinomas is currently under investigation. Of high recent interest is the possible addition of immune oncology agents such as the PD-1 or PD-L1 inhibitors. A recent report on the use of the PDL1 inhibitor durvalumab after completion of concurrent chemoradiotherapy in patients with unresectable stage IIIB disease has been reported as meeting its primary endpoint. It is likely that this and other studies will be relevant for superior sulcus tumors as well. Currently ongoing trials of increasing progression-free survival and their scientific basis will be reviewed.
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Author of
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P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
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P2.01-075e - Neutrophil to Lymphocyte Ratio Predicts Survival in Advanced NSCLC Patients Treated with Second-Line PD-1 Immune Checkpoint Inhibitors (ID 9091)
09:00 - 09:00 | Presenting Author(s): Philip Bonomi
- Abstract
Abstract not provided
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YI 01 - Young Investigator and First Time Attendee Session (ID 588)
- Event: WCLC 2017
- Type: Young Investigator
- Track: Education/Publication/Career Development
- Presentations: 1
- Moderators:Peter Goldstraw, Giorgio Vittorio Scagliotti
- Coordinates: 10/15/2017, 08:00 - 11:30, F201 + F202 (Annex Hall)
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YI 01.03 - Community versus Academic Oncology (ID 7847)
08:25 - 08:40 | Presenting Author(s): Philip Bonomi
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Relatively little information is available for hematology oncology fellows to inform their choice for an academic oncology(AO) vs a community oncology(CO) career. In 2006, Desch and Blayney(1) described practical differences between AO and CO careers which are still pertinent today. A more recent report from Vanderbilt(2) describes factors which appear to influence oncology fellows’ career decisions. Once a career path has been selected, does this choice affect career and work-life balance satisfaction? Shanafelt and his colleagues have described the impact of career choice and related factors on job satisfaction(3,4). This review will summarize the results of these reports and share a perspective regarding possible changes in oncology practices which could impact career choice. Desch and Blayney(1) describe mission, governance, patient care, financial considerations, referral bases, career flexibility, and determinants of success. The mission for community oncologists(COs) consists of delivering excellent patient care and running a successful business. In contrast, the mission for academic oncologists(AOs) encompasses patient care, research and teaching. CO governance offers more autonomy and usually consists of a doctor owned corporation with equal ownership. AOs work in a hierarchical system with multiple levels between the physician and senior leadership. There are significant differences in delivering patient care. Desch and Blayney point out that “ COs are intern, resident, fellow, and attending all rolled into one. ” COs have more weekend and night call. In addition, COs provide care for multiple types of cancer patients , while AOs’ practice is usually limited to one or two types of malignancy. Patient referrals for COs depend upon building relationships with primary care physicians and surgeons in their community. AOs also get patient referrals from primary care physicians and surgeons, but they rely heavily on institutional reputation, the reputation of disease specific experts, and a robust clinical trial program. Publishing and giving presentations at local and national meetings establishes AOs as disease specific experts which results in physician referrals and in patient initiated consultations. Revenue for COs depends upon fees for physician services, for administration of intravenous treatment , for laboratory tests, for imaging, and revenue from chemotherapy/immunotherapy treatments. For AOs, revenue comes from fees for physician services, grants, clinical trial revenue, and philanthropy. In some academic institutions, revenue may also come from the ancillary sources, similar to private practice. Starting and subsequent compensation is higher for COs who receive significant salary increases when they become full partners in the corporation, 2-5 years after joining the practice. Salary for AOs increases with increasing academic rank and may be supplemented with bonuses and honorariums for lectures and participation in advisory boards. Desch and Blayney(1) suggest that there are critical success factors for COs and AOs. . Building a reputation as a local expert and being readily available to referring MD’s and partners is essential for COs. . They also point out that it is essential for COs to invest time to understand bonuses and to show that they value and support the practice staff. AOs must focus on area of expertise, choose a good mentor, publish results of research, and apply for grants. It is not realistic to expect AOs with a large clinical practice to be the principal investigator on a grant. However, these clinicians can learn the concepts of basic science and partner with laboratory investigators in translational research grant proposals. Horn and her collegues(2) studiedfactors associated with selecting an AO or CO career. They invited program directors at 56 NCI designated and National Comprehensive Cancer Network cancer centers. Fellows at these institutions were asked to complete a questionnaire regarding their interest in AO vs CO careers. . Fellows with a high interest in AO were more likely to be women, have an additional graduate degree, and to have participated in basic research. Also fellows who were more interested in AO gave more presentations at scientific meetings and had more publications. Having an influential mentor and a desire to teach were also related to pursuing a career in AO. . Fellows who were more interested in CO were motivated by work-life balance and autonomy. This study suggest that fellows who are primarily motivated by being involved in identifying new information and teaching are more likely to pursue AO , while fellows who are motivated by favorable work-life balance and having more autonomy are more likely to pursue a CO career. How do practicing oncologists feel about their careers? Shanafelt and colleagues(3,4) have published two reports describing results of a survey which evaluated burnout, career satisfaction, life – work balance satisfaction and retirement. They(3) found that COs spent more time in clinic and saw more patients.. Younger age and more hours in clinic were associated with increased risk of burnout, which was defined as a combination of emotional exhaustion and depersonalization (loss of concern for patients),. There was a trend for higher rate of emotional exhaustion and a significantly higher rate of depersonalization in community oncologists. Although the majority of oncologists would choose a career in oncology, there was a higher number of COs who stated they would not choose an oncology career. In the second report(4), they did not compare AOs and COs. They saw that although most oncologists find meaning in their work, 52% were dissatisfied with work-life balance. “They like their work but want to do less of it.” Work-life balance was affected by more night and weekend call, while method of compensation salary +/- bonuses (most AOs) versus incentive (most COs) was not related work-life balance. For oncologists who planned to reduce work hours, the most common reason was to spend more time with family. In summary, when making a career choice, oncology fellows should identify what motivates them. I suspect that the majority of oncologists will continue to be happy with their career choice and that the current differences between AO and CO careers may decrease because more COs will be employed by hospital systems. References 1.Desch CE, Blayney DW. Making the Choice Between Academic Oncology and Community Practice: The Big Picture and Details About Each Career. Oncol Pract 2:132-138, 2006 2.Horn L, Koehler E, Gilbert J, et al. Factors Associated with the Career Choices of Hematology and Medical Oncology Fellow Trained ar Academic Insitutions in the United States. J Clin Oncol 29: 3932 - 3938, 2011 3.Shanafelt TD, Gradishar WJ, Kosty M, et al.Burnout and Career Satisfaction Among US Oncologists. J Clin Oncol 32: 678-686, 2016 4.Shanafelt TD, Raymond M, Kosty M, et al.Satisfaction with Work-Life Balance and the Career and Retirement Plans of US Oncologists.J Clin Oncol 32:1127-1135, 2014
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