Expert Consensus on Resection of Chest Wall Tumors and Chest Wall Reconstruction

Lei Wang; Xiaolong Yan; Jinbo Zhao; Chang Chen; Chun Chen; Jun Chen; Ke-Neng Chen; Tiesheng Cao; Ming-Wu Chen; Hongbin Duan; Junqiang Fan; Junke Fu; Shugeng Gao; Hui Guo; Shiping Guo; Wei Guo; Yongtao Han; Ge-Ning Jiang; Hongjing Jiang; Wen-Jie Jiao; Mingqiang Kang; Xuefeng Leng; He-Cheng Li; Jing Li; Jian Li; Shao-Min Li; Shuben Li; Zhigang Li; Zhongcheng Li; Chaoyang Liang; Nai-Quan Mao; Hong Mei; Daqiang Sun; Dong Wang; Luming Wang; Qun Wang; Shumin Wang; Tianhu Wang; Lunxu Liu; Gaoming Xiao; Shidong Xu; Jinliang Yang; Ting Ye; Guangjian Zhang; Linyou Zhang; Guofang Zhao; Jun Zhao; Wen-Zhao Zhong; Yuming Zhu; Karel W. E. Hulsewé; Yvonne L. J. Vissers; Erik R. de Loos; Jin Yong Jeong; Giuseppe Marulli; Alberto Sandri; Zsolt Sziklavari; Jacopo Vannucci; Luca Ampollini; Yuichiro Ueda; Chaozong Liu; Andrea Bille; Masatsugu Hamaji; Beatrice Aramini; Ilhan Inci; Cecilia Pompili; Hans Van Veer; Alfonso Fiorelli; Ricciardi Sara; Inderpal S. Sarkaria; Fabio Davoli; Hiroaki Kuroda; Servet Bölükbas; Xiao-Fei Li; Lijun Huang; Tao Jiang

Disclosures

Transl Lung Cancer Res. 2021;10(11):4057-4083. 

In This Article

Results and Discussion

Consensus 1: Wide Excision Should be Performed for Desmoid Tumor (DT) of Chest Wall (Category 1). After Excluding the Distant Metastasis by Multi-disciplinary Team, Solitary Plasmacytoma (SP) of Chest Wall can be Treated With Extensive Resection and Adjuvant Radiotherapy (Category 3)

First described by John Macfarlane in 1832,[7] DTs can be diagnosed in the abdomen, chest wall, scapular girdle, the pelvic girdle, and the distal ends of the lower limbs. Although DTs were identified as benign tumors at the outset due to the rarity of metastasis, they were prone to recur or invade even after wide resection. The pathological features of DTs differ significantly from malignant tumors; however, DTs are regarded as equivalent to low-grade sarcoma due to their tendency towards local invasion and frequent recurrence.[8] Therefore, the excision extension of DT has always been an argument of discussion.

DT is a relatively uncommon disease in clinical practice, with 7–10% of DTs occurring in the chest wall.[7] Thus, a standard of care is not achieved yet because many experts hold different positions on the final treatment option and clinical perspective.[2–6] In some studies, DTs of the chest wall were excluded from malignant lesions and the patients did not receive wide excision and adjuvant therapy.[8,9] However, many investigators consider DT of the chest wall as a low-grade sarcoma, and perform wide excision and chest wall reconstruction for these patients.[7,10–12] There are some explanations of these opposing academic views. One of the important reasons is that the margin status and resection thickness was not associated with DT recurrence in numerous studies.[13–15] However, since most of the studies were retrospective, single center analyses with a low level of evidence, final conclusions about margin status have not yet been determined in some clinical guidelines.[16] In this survey, 80.5% of surgeons agreed that DT of the chest wall should be treated as a malignant lesion with extensive resection. Wide excision with above 2 cm margin distance should be attempted to obtain a R0 resection margin for chest wall tumors. R0 surgical margin should be obtained as far as possible without compromising vital organ function, while R1 surgical margin can only be accepted if there is a risk of serious complications.

SP is one of the subtypes of multiple myeloma, including osseous and extraosseous diseases. SP is rare, and is characterized by a localized accumulation of neoplastic monoclonal plasma cells, without proof of systemic myelomatosis. SP represents less than 5% of all plasma cell neoplasms[17] and mostly occurs in the spine, pelvis, and pectoral girdle, while rarely occurring in the sternum, ribs, and clavicle.[17–19] According to the current clinical guidelines, radiotherapy with a 40–60 Gy is recommended as an initial standard therapy.[20] Surgery is permitted only when local osseous instability or serious nerve compression occurs. However, a few samples with solitary sternum plasmacytoma have previously received wide resection and chest wall reconstruction in clinical practice. Multiple articles present these surgical samples as case reports.[21,22] Sabanathan et al.[23] presented 17 SPs in the chest wall treated by radical excision, and seven of these progressed to multiple myeloma within 2 years of surgery. Also, the 5-year survival rate of 59% was similar to that reported in previous studies.[24,25]

Furthermore, a cohort of six patients with solitary sternum plasmacytoma in Tangdu Hospital (Shaanxi Province, China) received wide excision and adjuvant chemotherapy, and obtained a median recurrence-free survival of 36 months.[26] Of these patients, three developed to multiple myeloma, and one patient died of the disease. Most of the reported cases that received wide excision are retrospective studies with small sample sizes. Despite complete resection of the local disease, disease free survival was not improved by excision and the long-term survival depended on the subsequent development of multiple myeloma. Due to the lack of high-level clinical evidence, the role of surgery for chest wall plasmacytoma remains controversial. In this survey, 54.8% of the surgeons agreed that SP of chest wall should be treated with extensive resection, and 32.1% of them considered the radiotherapy as the first treatment for SP of chest wall. In addition, 13.1% of the surgeons were not sure about the issue. A multi-disciplinary team is necessary before surgery, including medical oncology, hematology, radiotherapy. The positron emission tomography-computed tomography (PET-CT) and bone marrow puncture must be performed to exclude the distant metastasis of disease before surgery. Given the systemic nature of plasmacytoma, adjuvant radiotherapy is recommended in clinical practice.[27] The adjuvant chemotherapy is a controversial issue due to the insufficient clinical evidence and it is recommended only in case of persistent disease on PETCT after radiotherapy.[27]

Consensus 2: Wide Excision With Above 2 cm Margin Distance Should be Attempted to Obtain a R0 Resection Margin for Chest Wall Tumors (Category 1). Given the Difficulty Of Reconstructive Surgery for Adjacent Organs, Including the Great Vessels, Heart, Trachea, Joints, and Spine, it is Unnecessary to Obtain Enough Resection Margin Distance if the Chest Wall Tumor Involves These Vital Organs (Category 2). However, the Tissue Adjacent to the Chest Wall Tumor (e.g., a Layer of Fascia) Should be Removed as Much as Possible. As for Manubrium Sterni Tumors, Capsula Articularis Sternoclavicularis can be Used as a Safe Margin Marker if the Tumor Does not Invade the Joint Capsule (Category 2)

Radical resection with a R0 margin is the standard surgical treatment for most tumors. However, the relationship between R0 resection margin and prognosis of chest wall sarcoma is controversial. In a number of previous retrospective studies,[28–31] wide excision of chest wall sarcomas was entirely unrelated to tumor recurrence and patient survival. However, other studies reported that patients with wide excision achieved lower recurrence rates and longer survival.[9,32–34] It remains contentious whether wide excision can translate into better survival outcomes for patients, as it often means increased surgical difficulty, postoperative complications, and greater clinical costs. As the above studies were single-center, retrospective, small-sample studies with a low level of clinical evidence, the final conclusions need to be further verified. In this survey, 71.4% of the surgeons deemed that wide excision was a key predictor of recurrence and survival for patients with chest wall tumors, and 22.6% of them were not sure whether wide excision can translate into better survival outcomes for patients. Moreover, 6% of the surgeons considered that wide excision was of no use to the patient. Some potential reasons can be summarized as follows. Multiple pathological types of chest wall tumor result in significant heterogeneity in the previous studies. Also, the pathological types included in previous studies vary greatly, and the skill level of the surgeons varied too. Moreover, the small sample size is also an important factor affecting the research results.

Although most surgeons can agree on R0 resection for chest wall tumors, the detailed value of surgical margin distance remains controversial. King et al.[33] regarded 4 cm on all sections of chest wall tumors as a surgical margin distance, and claimed necessity to remove one rib on each of the upper and lower margins of the tumor. The 5-year recurrence rate of patients in the 4 cm margin group (29%) was lower than that of the 2 cm margin group (56%), but the difference was not statistically significant. In some studies, patients with a surgical margin of 2 cm can also achieve a good survival prognosis.[35,36] Park et al. believed that patients with a surgical margin of 1.5 cm could also obtain a good prognosis.[32] In clinical practice, the larger the tumor diameter, the more difficult it is to achieve wide excision. Especially for sternal sarcoma, wide excision often requires resection of the adjacent pericardium, thymus, great blood vessels, and other important organs. The larger the defect, the more difficult the reconstruction surgery. Thus, in cases where the reconstructive surgery cannot be performed, including the great blood vessels and heart, a positive surgical margin (R1) is permissible. In these cases, postoperative radiotherapy should be considered.

In this survey, 51.2% of surgeons believed that the margin distance of 2–3 cm should be guaranteed during the wide excision. Also, 20.2% of surgeons thought that a margin distance of 3–4 cm should be guaranteed, while 13.1% of them considered that the margin distance of 4–5 cm should be obtained. Notably, 69.84% of surgeons deemed that it was not necessary to achieve a sufficient distance on all the tumor margins. R1 margin can be acceptable if the chest wall tumor is located next to vital organs, including the great vessels, heart, trachea, joints, and spine.

As for manubrium sterni tumors, 76.19% of surgeons believed that capsula articularis sternoclavicularis can be used as a safe margin marker if the tumor does not invade the joint capsule. With respect to the excision of skin adjacent to the tumor, 41.3% of thoracic surgeons thought that the skin on the surface of the tumor was still widely excised, even though the imaging and palpation examinations did not indicate the invasion of skin, and the excision extension was based on ensuring the incision suture.

Consensus 3: For Patients With Chest Wall Tumors Undergoing Unplanned Excision (UE) for the First Time, it is Necessary to Carry out Wide Excision as Soon as Possible Within 1–3 Months Following the Previous Surgery (Category 1). Wide Excision With Above 2 cm Margin Distance Should be Attempted to Remove the Residual Tumor (Category 1). Adjuvant Radiotherapy or Systemic Chemotherapy can be Performed According to the Specific Situation of Re-resection (Category 3)

It is not uncommon for a surgeon to operate on a presumed benign soft tissue mass without appropriate preoperative imaging or prior biopsy, and then to excise the lesion without attention to the surgical margins. Such surgery has been termed an ''unplanned excision'' or "whoops" procedures.[37,38] Most UEs are performed by surgeons without specialty training in oncology, especially in primary hospitals. After unplanned surgery, it is difficult to make the next decision once the patient is diagnosed with a malignant tumor. There is controversy as to whether UEs result in higher recurrence and survival rates. Some previous studies have shown that UEs of local soft tissue sarcomas had no significant effect on disease-specific and metastasis-free survival compared with those with planned excisions.[39,40] By contrast, several previous studies emphasized the problems of an UE, showing the higher incidence of local recurrence even after the residual tumor was removed in re-resected specimens.[38,41–43] In an analysis of 295 patients with soft tissue sarcoma that underwent expanded re-resection of the tumor bed, residual neoplasms were visible to the naked eye in 28% of patients, while microscopically-visible residual tumors were present in 46% of patients.[4,44] The 5- and 10-year recurrence-free survival rates of patients who underwent re-resection were significantly higher than that of patients who did not undergo expanded re-resection.[4,44] However, chest wall sarcoma is a small percentage of these cases; thus, the level of evidence supporting these conclusions is low.

In addition, the optimal time for reresection has not yet been determined. It is difficult to evaluate the anatomical location of the primary chest wall tumor during re-operation, especially the surgical margins of skin and soft tissue, which may lead to misestimation of the resection range. In this survey, 82.2% of surgeons believed that the re-resection procedure should be carried out within 1–3 months after unplanned resection. Moreover, 73% of the surgeons believed that a margin distance of 2–4 cm should be guaranteed during the re-resection procedure, while 16% of them considered that a margin distance of 4–5 cm should be obtained. Also, 50% of surgeons agreed to perform local radiotherapy in the tumor bed or chemotherapy.

Consensus 4: Current Tumor-node-metastasis (TNM) Staging Criteria (American Joint Committee on Cancer, AJCC) of Bone Tumor and Soft Tissue Sarcoma (Trunk and Extremities) are not Suitable for Chest Wall Sarcomas, and it is Necessary to Develop new Staging Criteria for Chest Wall Sarcomas (Category 2). Depending on the Location of the Chest Wall Sarcoma, Lymphnode Dissection may be Performed in the Surgically Visible Area or Adjacent Mediastinal Area (Category 3)

Due to the low incidence of chest wall sarcoma and the lack of high-level clinical evidence, there is currently no TNM staging of chest wall sarcoma. Some osseous tumors, including osteosarcoma, chondrosarcoma, Ewing sarcoma, osteoclastoma, must be staged according to the 8th edition TNM staging criteria of bone tumors (trunk, extremities, skull, and maxillofacial).[5] Some soft tissue sarcomas, including leiomyosarcoma, synoviosarcoma, fibrosarcoma, primitive neuroectodermal tumor, hemangiosarcoma and so on, can be staged according to the 8th edition TNM staging criteria of soft tissue sarcomas (trunk and extremities).[4]

However, there are many significant differences between the two staging systems, especially with regards to the T staging criteria. In the TNM staging criteria of bone tumors (trunk, extremities, skull, and maxillofacial), the tumor is divided into T1 (≤8 cm), T2 (>8 cm), and T3 (discontinuous tumor), with a cut-off of 8 cm. In the TNM staging criteria of soft tissue sarcomas (trunk and extremities), the tumor is divided into T1 (≤5 cm), T2 (5–10 cm), T3 (10–15 cm), and T4 (>15 cm), with cut-off of 5, 10, and 15 cm, and also considers tumor location (deep versus superficial) and histological grade. In one of the main references for the establishment of the two staging criteria, sarcomas in extremities (60%) were mainly included, while sarcomas in the trunk (20%) were encountered less, and there was no grouping of chest wall sarcomas due to the small sample.[45]

Notably, the anatomy of the extremities and chest wall differs greatly. Osteogenic and chondrogenic sarcomas in the chest wall with a diameter of 8 cm often invade 2–3 adjacent ribs, the pleura, lung, great vessels, and other organs, but the current T1 staging may underestimate the severity of the disease. Referring to the other tumors, it may be inaccurate to determine the extent of tumor invasion only by diameter. In addition, due to the low incidence of lymph node metastases in sarcomas, the current guidelines do not specify lymph node dissection. However, there are numerous lymph nodes surrounding the chest wall sarcomas adjacent to the anterior mediastinum. Although Riad et al. reported lymph node metastasis in 3.7% of patients with soft tissue sarcomas of the extremities, but lymph node metastasis of chest wall sarcoma has not yet been investigated.[4,46]

In this survey, 76.5% of surgeons believed that the current TNM staging criteria of bone tumor and soft tissue sarcoma were not suitable for chest wall sarcomas and it is necessary to set special staging criteria for chest wall sarcomas. Additionally, 58.7% of surgeons believed that lymph node dissection should be performed in the visible area or adjacent mediastinal area.

Consensus 5: It is Necessary to use Rigid Implants for Chest Wall Reconstruction for Chest Wall Defect Exceeds 5 cm in Adults (Category 2) and Adolescents (Category 3). Titanium Plate and Mesh Polymethylmethacrylate are the Most Commonly Used Rigid Implants. Personalized Implants, Such as Three-dimensional Printed Implants, Have the Advantage of Anatomically Repairing the Chest Wall Defect

Traditionally, chest wall defects larger than 5 cm in maximum diameter should be reconstructed with rigid implants to prevent chest wall floating, paradoxical breathing, and/or respiratory failure.[47,48] The chest wall defects adjacent to the scapula should be reconstructed with rigid implants if the maximum diameter of the defect exceeds 10 cm.[47,48] However, the above views are mainly based on the surgical experience and consensus of clinicians, and there is still a lack of high-level clinical evidence confirming them.

In addition, for adolescent patients with chest wall tumors, the long-term survival should be considered after wide excision, and development of postoperative scoliosis must be afforded greater attention. Several studies have shown that approximately 20–30% of adolescent patients with chest wall wide excision develop scoliosis in 5–10 years after surgery.[49–52] The use of flexible materials such as a mesh for chest wall reconstruction can increase the compliance of the chest wall, which may increase the risk of scoliosis. Therefore, the use of rigid implants for chest wall reconstruction is recommended.[52] However, the use of rigid implants for chest wall reconstruction may cause postoperative restriction on the growth of the thorax; thus, many doctors are very cautious about the use of rigid implants for adolescents with chest wall defects.

There are various types of rigid implants in clinical practice, including Matrix-RIB (DePuy Synthes, West Chester, PA), STRATOS (Strasbourg Thoracic Osteosyntheses System, MedXpert GmbH, Heitersheim, Germany), Ribfix Blu (Zimmer Biomet) and Sternalock (Zimmer Biomet), titanium mesh, polymethylmethacrylate, personalized implants, etc.[53–57] The selection of implants is mainly based on the surgical experience, and there are no relevant clinical studies comparing the repair effects of the mentioned implants. The three-dimensional printed (3DP) implants have the advantage of anatomically repairing the chest wall defect, with very good clinical application potential.[56,57] Numerous medical centers have carried out chest wall reconstruction using these implants, which is one of the important progresses in the field of chest wall reconstruction in recent years.[56–61] Multiple biomaterials can be fabricated as 3DP implants, including titanium, polyether-ether-ketone (PEEK), and polycaprolactone. Titanium is the most common implant material in clinical practice, but the excessive elasticity modulus of titanium may have a stress-shielding effect on bone growth. PEEK has an elastic modulus close to that of cortical bone, but the hydrophobic interface of PEEK may affect bone fusion.

However, 3DP implants come with skill requirements for surgeons and engineers, who require tacit cooperation in the process of implant design, production, and surgery to achieve ideal clinical effects.[57] 3DP implants have not yet been approved by the State Food and Drug Administration (FDA) or the National Medical Products Administration of China, and surgery can only be carried out as part of clinical studies in a few medical centers. In this survey, 71.4% of the surgeons always use rigid implants for chest wall reconstruction if the maximum diameter of chest wall defect exceeds 5 cm; 47.6% of them use titanium implants, including Matrix-RIB, STRATOS, and titanium mesh, while 15.4% of them use polymethylmethacrylate and other implants. Also, 50.8% of thoracic surgeons considered it necessary to use rigid implants to reconstruct chest wall defects in adolescent patients. With respect to the selection of reconstruction materials, 82.5% of the surgeons had used synthetic mesh and biological mesh, including polypropylene mesh, polylactic acid mesh, nylon mesh, polytetrafluoroethylene (PTFE) mesh, silicone membrane mesh, silicone membrane mesh, bovine pericardium mesh, porcine mesentery mesh, artificial skin, etc.

Consensus 6: For NSCLC Invading the Chest Wall, Wide Excision is Recommended for Patients With Stage T3–4N0–1M0 (Category 2). As for NSCLC Without Lymph Node Metastasis (Stage T3–4N0M0), the Treatment Mode of Surgery (Category 2) + Adjuvant Chemotherapy (Category 3) ± Radiotherapy (Category 3) is Recommended. As for NSCLC With Hilar Lymph Node Metastasis (Stage T3–4N1M0), the Treatment Mode of Neoadjuvant Chemotherapy (Category 2) ± Radiotherapy (Category 2) + Surgery (Category 2) is Recommended

NSCLC invading the chest wall is a rare clinical disease. According to the TNM staging criteria in the 8th edition of the NCCN NSCLC Clinical Practice Guidelines, NSCLC invading the chest wall can be classified as stage T3 or T4. A number of retrospective clinical studies have shown that patients with NSCLC invading the chest wall can benefit from surgery, especially those without lymph node metastasis.[62–69] Patients with NSCLC invading the chest wall (stage T3–4N0M0) can achieve a 5-year survival rate of 30–67%.[62–69] However, most of the above studies were retrospective, single-center, and small-sample studies with a low level of clinical evidence. Thus, in the NCCN and Chinese Society of Clinical Oncology guidelines, surgery is only recommended as level 2 evidence for patients with NSCLC invading the chest wall (stage T3–4N0M0).[70]

R0 resection and lymph node invasion are the major prognostic factors for NSCLC invading the chest wall. In this survey, 76.2% of surgeons agreed to carry out a wide excision for patients with NSCLC invading the chest wall without lymph node metastasis (stage T3–4N0M0), and 50.8% of them continued to administer adjuvant chemotherapy and/or radiotherapy. Also, 66.6% of surgeons agreed to perform a wide excision for patients with NSCLC invading the chest wall with hilar lymph node metastasis (stage T3–4N1M0), while 62.6% administered neoadjuvant chemotherapy and/or radiotherapy preoperatively. Only 17.5% of surgeons considered operating on patients with NSCLC invading the chest wall with mediastinal lymph node metastasis (stage T3–4N2M0). Wide excision with above 2 cm margin distance aiming for R0 resection should be attempted to achieve an en bloc resection.

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