Pancoast Syndrome

Practice Essentials

Pancoast syndrome (Pancoast’s syndrome) typically results when a malignant neoplasm of the superior sulcus of the lung leads to destructive lesions of the thoracic inlet and involvement of the brachial plexus and cervical sympathetic nerves (stellate ganglion).^{[1, 2, 3, 4]} This is accompanied by the following:

• Severe pain in the shoulder region radiating toward the axilla and scapula, with later extension along the ulnar aspect of the arm to the hand
• Atrophy of hand and arm muscles
• Horner syndrome (ptosis, miosis, hemianhidrosis, enophthalmos)
• Compression of the blood vessels with edema

Most Pancoast tumors are non–small cell lung cancer (NSCLC])—specifically, squamous cell carcinoma (SCC) or adenocarcinomas; only 3-5% are small cell carcinomas. Squamous cell carcinoma occurs more frequently, although large cell and undifferentiated types are also common. Adenocarcinoma is sometimes found in this location and can even be metastatic. Involvement of the phrenic or recurrent laryngeal nerve or superior vena cava obstruction is not representative of the classic Pancoast tumor.

Once universally fatal, Pancoast tumors are currently treatable with outcomes similar to those of other stage-matched non–small cell lung cancers.^[5] Careful assessment and appropriate staging are performed before surgery, and selected patients are administered preoperative irradiation of 30 Gy over 2 weeks. After an interval of 2-4 weeks, surgical resection of the chest wall and lower brachial plexus and en bloc lung resection produces a 5-year survival rate of 30%. Contraindications to surgical management include the following:

• Extension of the tumor into the neck or vertebrae
• Presence of substantial mediastinal lymph nodes
• Peripheral tumor dissemination

Protocols that use combinations of radiation therapy, chemotherapy, and surgery are currently being studied to determine the best therapy.

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Pathophysiology

Pancoast tumors are a subset of lung cancers that invade the apical chest wall. Because of their location in the pleural apex, they invade adjoining tissue. Although other tumors may have a similar clinical presentation because of their location at the thoracic inlet, the most common cause is believed to be a bronchogenic carcinoma arising in or near the superior sulcus and invading adjacent extrathoracic structures by direct extension. Location, rather than pathology or histology of origin, is significant in producing the tumor’s characteristic clinical pattern.^[6]

The bulk of a true Pancoast tumor is extrathoracic, originating in an extreme peripheral location with a plaquelike extension over the lung apex and principally involving the chest wall structures rather than the underlying lung parenchyma. Bronchogenic carcinomas occurring in the narrow confines of the thoracic inlet invade the lymphatic vessels in the endothoracic fascia and include, by direct extension, the following structures:

• Intercostal nerves
• Lower roots of the brachial plexus
• Stellate ganglion
• Sympathetic chain
• Adjacent ribs and vertebrae.

Carcinomas in the superior pulmonary sulcus produce Pancoast syndrome, thus causing pain in the shoulder and along the ulnar nerve distribution of the arm and hand.^[7] (These carcinomas also cause Horner syndrome.) These apical lung tumors tend to be locally invasive early. In the absence of metastases and regional nodal involvement, these apical cancers can be successfully treated.

The tumor may invade the bony structures of the chest, including the first or second thoracic vertebra or the first, second, or third rib. In a review of 60 patients with Pancoast tumors, Maggi et al found radiographic evidence of rib erosion in 50%; an almost equal percentage demonstrated involvement of the first or second rib, and 20% had involvement of the third rib. One patient had involvement of all 3 ribs.^[8]

The tumor can also invade the first or second thoracic vertebral bodies or intervertebral foramina. From this point, it can extend to the spinal cord and result in cord compression. The subclavian vein or artery may also be invaded.

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Etiology

The overwhelming majority of cases of Pancoast syndrome are non–small cell lung carcinoma (NSCLC), with more than 95% located in the superior sulcus. The most common varieties are SCC and adenocarcinoma; large cell carcinoma has also been reported.

Although quite rare (responsible for fewer than 5% percent of cases in most series), small cell carcinoma is also observed. Maggi et al reported small cell carcinoma in only 3 of the 60 patients in their series.^[8] More typically, small cell carcinoma manifests in a central rather than a peripheral location.

Although NSCLC is by far the most common cause of Pancoast syndrome, the list of differential diagnoses is broad. Because of the wide variety of diseases that can produce Pancoast syndrome, a histologic diagnosis is mandatory before definitive treatment is initiated.

Rare causes include the following:

• Desmoid tumors^[9]
• Hemangiopericytoma^[10]
• Adenoid cystic carcinoma^[11]
• Metastatic carcinoma^[12]
• Lymphoma^[13]
• Thyroid carcinoma^[14]
• Bacterial^{[15, 16]} and fungal infections^{[17, 18]}
• Lymphomatoid granulomatosis
• Vascular aneurysms
• Amyloid nodules
• Cervical rib syndrome
• Inflammatory pseudotumor (plasma cell granuloma)
• Mycotic subclavian artery aneurysm
• Carotid pseudoaneurysm in a child (caused by a hydatid cyst)

Risk factors are similar for almost all lung cancers and include the following:

• Prolonged asbestos exposure
• Exposure to industrial elements (eg, gold, nickel)
• Tobacco smoking
• Secondary smoke exposure

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Epidemiology

Overall, Pancoast tumors are much less common than other lung cancers, accounting for fewer than 5% of these cancers (1-3% in various previous series).^{[19, 20]} Originally deemed universally fatal, Pancoast tumors are now amenable to curative treatment because of improvements in combined modality therapy and development of new techniques for resection.

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Prognosis

The prognosis for patients with Pancoast syndrome is stage dependent. Adverse prognostic factors include the following:

• Presence of Horner syndrome
• Involvement of mediastinal lymph nodes
• Incomplete resection
• Involvement of supraclavicular lymph node
• Vertebral body invasion

To date, no patient with the first 3 prognostic factors has survived for 5 years.

Distant disease limits survival. Treatment failure is especially frequent in patients with involvement of the brain. The authors recommend careful surveillance for brain metastasis during and after the therapy. The authors also recommend obtaining brain imaging prior to surgery in patients receiving induction therapy for the primary tumor.

Mortality and survival

Attar et al reported a median survival of 36.8 months in patients with T3 lesions undergoing combined modality treatment; median survival was only 6.4 months if the patient had T4 disease.^[21]

Overall survival data were summarized by Detterbeck, who noted that 5-year survival rates ranged from 15% to 56%.^[22] Of the 104 patients treated by Attar and coworkers, 7 (~7%) were 5-year survivors and 3 (~3%) were 10-year survivors.^[21] Another study demonstrated surgical morbidity rates of 7-38%, with mortality ranging from 5% to 10%.^[23]

For neoplastic causes, predictors of 5-year survival are weight loss, supraclavicular fossa or vertebral body involvement, disease stage, and surgical treatment. A study by an MD Anderson group reported the following findings^[24] :

• For patients with stage IIB disease, the 5-year survival rate was 47%, whereas for those with stage IIIA and IIIB disease, it was 14% and 16%, respectively
• In patients with stage IIB disease, surgical treatment and weight loss were significant independent predictors of 5-year survival
• Among patients with stage IIIA disease, the only predictor of survival was the Karnofsky performance score
• In patients with stage IIIB disease, the only independent predictor of survival was a right superior sulcus location, which was associated with a worse 5-year survival rate than a left superior sulcus location
• Compared with patients who had squamous cell tumors, more patients with adenocarcinoma had cerebral metastases within 5 years

Relapse

Locoregional relapse is common despite preoperative or postoperative radiation therapy. Muscolino et al found locoregional recurrence in 60% of patients treated with a combined radiosurgical approach. Ginsberg et al found that 94 of their 124 patients had recurrence of disease, with 72% of these cases being locoregional at initial recurrence. In two thirds of patients who underwent complete resection, local recurrences were the first site of relapse.^[19]

This distribution of relapses was noted in several studies reviewed by Detterbeck. In many of these studies, patients received preoperative radiation therapy.^[22] In the Memorial Sloan-Kettering experience, additional postoperative brachytherapy was administered to achieve maximal possible local control; despite these measures, local relapses and, ultimately, distant relapses were frequent.^[19]

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History

Patients with Pancoast syndrome may present with referred pain over the scapula to the shoulder as the result of damage to the afferent pain fibers of the sympathetic trunk. The symptoms are typical of the location of the tumor in the superior sulcus or thoracic inlet adjacent to the eighth cervical nerve roots, the first and second thoracic trunk distribution, the sympathetic chain, and the stellate ganglion.

Initially, localized pain occurs in the shoulder and vertebral border of the scapula. Pain may later extend along an ulnar nerve distribution of the arm to the elbow and, ultimately, to the ulnar surface of the forearm and to the small and ring fingers of the hand (C8). If the tumor extends to the sympathetic chain and stellate ganglion, Horner syndrome and anhidrosis develop on the ipsilateral side of the face and upper extremity.

The pain is frequently relentless and unremitting, and adequate relief often requires administration of narcotics. The patient usually supports the elbow of the affected arm in the hand of the opposite upper extremity to ease the tension on the shoulder and upper arm.

The hand muscles may become weak and atrophic, and the triceps reflex may be absent. The first or second rib or vertebrae may be involved by tumor extension and intensify the severity of pain. The spinal canal and spinal cord may be invaded or compressed, with subsequent symptoms of spinal cord tumor or cervical disk disease.

Many patients are initially treated for presumed local musculoskeletal conditions such as bursitis and vertebral osteoarthritis with radicular pain. Symptoms may persist for many months before evaluation for progression reveals the cause. In a 1994 series by Maggi et al, symptoms lasted 2-36 months, with a mean of 9.7 months.^[8] In 1997, Muscolino described plexopathy or radicular symptoms in 53% of 15 patients.^[25]

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Physical Examination

Physical examination of patients with Pancoast tumor may reveal findings consistent with Horner syndrome, such as ptosis and miosis, which result from paralysis of the dilating sympathetic fibers. Supraclavicular lymphadenopathy may also be observed.

Horner syndrome (Horner’s syndrome) is the result of invasion of the lower cervical and first thoracic ganglia, which frequently fuse into a single ganglion, the stellate ganglion. Horner syndrome is observed in 20-50% of patients at presentation.^{[19, 8, 25, 21]} Decreased sweating on the affected side and ptosis of the denervated lid may be observed. Application of topical cocaine to the miotic eye (contracted pupil) fails to cause pupil dilation, while appropriate dilation is noted in the unaffected eye.^[26]

Cough, dyspnea, and hemoptysis, which are signs often associated with lung cancer, are not as common in individuals with Pancoast syndrome because of the peripheral location of the tumor. When present, they are associated with a worse prognosis. Also uncommon but occasionally noted are more advanced tumors with involvement of the recurrent laryngeal nerve, phrenic nerve, or superior vena cava.

Infrequently, a patient with a Pancoast tumor may also have features of a paraneoplastic syndrome. Most of the metabolic manifestations are the result of the secretion of endocrine chemicals by the tumor. Manifestations encompass Cushing syndrome, excessive antidiuretic hormone secretion, hypercalcemia, myopathies, hematologic problems, and hypertrophic osteoarthropathy. The presence of paraneoplastic syndromes does not connote unresectability, but most of these are associated with small cell cancer.

Brain metastasis may be relatively common at the point of diagnosis and indicates an increased risk for treatment failure. Preoperative brain imaging studies are highly recommended in patients who are receiving induction therapy for the primary tumor in the superior sulcus.^[27]

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Approach Considerations

Imaging and biopsy are the cornerstones of evaluation of Pancoast syndrome. The apex of the lung can be difficult to investigate because it is bounded laterally by the first rib, posteriorly by the first rib and the vertebral bodies, and anteriorly by the costal cartilage of the first rib and the manubrium. Plain radiographs of the chest frequently show no change or an asymmetry or thickening of the apical cap. Apical lordotic films may be more revealing. Computed tomography (CT) and magnetic resonance imaging (MRI) have become standard. Liver, bone, and brain scans are performed to look for metastatic disease.

In very rare cases, sputum cytology has been helpful. Initially, most Pancoast tumors are diagnosed histologically on the basis of transthoracic needle biopsy results. Diagnosis via bronchoscopy is less helpful because most of these tumors are peripherally located. The flexible scope is more useful than the rigid scope in obtaining bronchoscopic aspirates and brush biopsy specimens.

Although more than 90% of patients can be correctly diagnosed on the basis of clinical and radiologic findings alone, open biopsy for pathologic validation may be performed through a supraclavicular incision. Results from a needle biopsy through the supraclavicular or posterior triangle are also successful in confirming the diagnosis and in delineating the cell type before treatment. Even though clinical diagnosis is relatively simple, performing a tissue biopsy is still necessary.

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Laboratory Studies

The blood workup for patients with Pancoast tumors is not specific, and results are not diagnostic.

Lung cancers produce various substances. Elevated levels of oncofetal carcinoembryonic antigen and beta-2 microglobulins are associated with many lung cancers. Unfortunately, these findings are not diagnostic, because levels of these chemicals are also elevated by other nonspecific causes, such as smoking and bronchitis.

Tumor markers (eg, bombesin, neuron-specific enolase, and other peptides) are common with small cell cancers and are related to the stage of the disease. They may aid in distinguishing differentiated forms of lung cancer from undifferentiated forms.

Various tumor oncogenes, including K-ras, c-myc, TP53, and HER-2/neu, have also been identified in patients with lung cancers. Although the presence of these oncogenes has some prognostic value, they are not important for staging of the cancer.

Routine blood work in all patients with a lung cancer includes a complete blood count (CBC) count, blood urea nitrogen (BUN) and creatinine levels, a white blood cell (WBC) count, and urinalysis. Coagulation parameters, such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet count, are appropriate. Unless metastatic disease is evident, liver function tests are not regularly performed. Any patient deemed a surgical candidate has blood drawn for a cross-match.

Urinalysis is performed in all patients before surgery, and a catheter specimen is obtained in women if the initial urinalysis result suggests contamination.

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CT, MRI, and PET

CT and MRI of the neck, chest, and upper abdomen have largely replaced older radiographic studies in the workup of Pancoast syndrome.

CT is less expensive than MRI and much more available. It can help assess bone destruction and is useful in general imaging of the lung for the evaluation of mediastinal adenopathy, other pulmonary nodules, and liver involvement. CT scanning helps identify invasion of the brachial plexus, chest wall, and mediastinum, as well as reveal involvement of the vena cava, trachea, and esophagus. Contrast CT scanning is useful for assessing subclavian vessel involvement.

MRI is useful for evaluating resectability. It may be more accurate in evaluating chest wall invasion, examining vascular structures, and assessing the brachial plexus for invasion.^{[28, 29, 30]} It is more accurate than CT for assessing invasion of cervical structures and vertebral bodies.

MRI has no advantage over CT in the evaluation of the mediastinum. In fact, CT is much better than MRI for assessing the mediastinum for lymph node involvement. Rib or transverse process involvement is not a sign of inoperability; however, involvement of the vertebral body makes achieving an adequate margin of resection very difficult and reduces the odds for survival.

Additional staging studies should be considered. Mediastinoscopy should be performed to evaluate mediastinal nodes. The presence of N2 mediastinal lymphadenopathy has a significant adverse effect on survival. CT or MRI of the head to exclude occult metastasis should be performed if treatment with curative intent is planned. CT of the chest can be extended to include the liver and adrenal glands.

Positron-emission tomography (PET) scanning is approved by the US Food and Drug Administration for the staging of non–small cell lung cancer in general, and it is increasingly being used in the setting of Pancoast syndrome.

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Chest Radiography

Chest radiographs may reveal a small homogenous apical cap or pleural thickening; they may show a thin plaque at the lung apex in the area of the superior sulcus or may reveal a large mass, depending on the stage of the tumor when it is first diagnosed. Suggestive films should prompt the astute diagnostician to order apical lordotic views for better visualization of the area.

Bone destruction of the posterior 1-3 ribs may sometimes be apparent. Rib invasion or vertebral body infiltration may be evident on a plain chest radiograph. Mediastinal enlargement may be apparent.

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Bronchoscopy and Biopsy

Bronchoscopy helps evaluate the tracheal and bronchial lumens; however, because most Pancoast tumors are peripheral, the diagnostic yield is low. Fiberoptic bronchoscopy has a higher yield than sputum cytology, which has positive results in fewer than 15% of patients,^[31] but bronchoscopy findings are positive in only 20-30% of patients, because of the peripheral location of the tumor.^[32] Bronchoscopy, however, can be useful in excluding otherwise unsuspected concurrent endobronchial lesions.

Tissue diagnosis is obtained on the basis of results from percutaneous needle biopsy, performed under either fluoroscopy or CT guidance. Staging is based on results of scalene node biopsy from palpable nodes or mediastinoscopy findings. If a patient presents with supraclavicular lymph node enlargement, then a fine-needle aspiration (FNA) biopsy of enlarged supraclavicular lymph nodes or an ipsilateral supraclavicular fullness procedure is a fast, safe, and inexpensive means of confirming the diagnosis.

Transthoracic needle biopsy by CT guidance has a high yield, up to 95% in some series.^{[33, 31, 34]} Some tumors may be evaluated only by thoracotomy, either open or video assisted.

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Other Tests

Rarely, arterial or venous involvement of the subclavian artery or vein occurs; thus, arteriography or phlebography may be helpful. This is usually accomplished in a retrograde fashion, although it can be approached from the opposite extremity or from the leg.

Baseline electrocardiography (ECG) is performed on all patients for comparison to postoperative ECG tracings (if one is performed).

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Staging

Pancoast tumors are staged using the tumor-node-metastasis (TNM) system of the International System for Staging Lung Cancer, adopted by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC).^[35] This classification stages lung cancers in terms of tumor characteristics and tumor distribution.

The T designation describes the size and invasiveness of the primary tumor. T3 indicates a tumor of any size that invades the chest wall (the parietal pleura). T4 is a tumor of any size that invades the vertebral body, a neural or vascular structure, the mediastinum, the esophagus, or the trachea.

The N designation describes the distribution of positive lymph nodes. N1 indicates metastasis to ipsilateral peribronchial or hilar nodes. N2 indicates the spread to ipsilateral mediastinal or subcarinal nodes. N3 indicates metastasis to nodes of the contralateral hilar and mediastinal areas or to scalene or supraclavicular nodes, either ipsilateral or contralateral.

The M designation describes the extent of distant metastasis. M0 indicates no identifiable metastatic disease, and M1 designates the presence of distant metastasis (eg, to brain, bone, or liver). Any M1 findings indicate stage IV disease.

Staging is determined by the location of the lesion and its metastases. A true Pancoast tumor is usually T3, reflecting extension of the tumor through the visceral pleura into the parietal pleura and the chest wall; it is classified as T4 when mediastinal invasion, cervical invasion, or both have occurred (see the Table below). Peripheral metastases signal a poor prognosis, and surgery is contraindicated in such cases.

Table. AJCC/UICC Stages for Pancoast Tumors.

View Table

See Table

Mediastinoscopy is used for staging to delineate the metastases to mediastinal lymph nodes. Cervical mediastinoscopy is indicated for right pulmonary lesions; a Chamberlain procedure (left second interspace mediastinoscopy) is indicated for left pulmonary lesions. Generally, mediastinoscopy is performed if the lymph nodes appear larger than 1 cm in diameter on a CT scan because the accuracy of CT for predicting metastatic involvement in enlarged lymph nodes is only 70%.

Conversely, if the CT scan does not reveal any enlarged lymph nodes, the patient is deemed operable. If the nodes in the mediastinum are positive, the prognosis is poor. The exception to this rule is an upper-lobe lesion with positive nodes on the right side of the trachea only. If these are internodal, spread is considered local, and the tumor may still be resectable.

Attar et al, reviewing their experience with 105 patients treated from 1955 to 1997, found that 30% of patients presented with T3 N0 disease (stage IIB), 26% with T4 N0 (stage IIIA), and 25% with metastatic disease (M1, stage IV).^[21] In their review of 124 patients, Ginsberg et al found that 58% of patients had T3 N0 disease, 16% had T3 N2, and only 1% had T3 N1; in addition, 6% of patients had T3 N3 disease, 18% had T4 N0, and 1% had T4 N.^[19]

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Approach Considerations

Pancoast tumors were once considered universally fatal. However, improvements in combined modality therapy and the development of new techniques for resection have made curative treatment possible for these tumors.^{[5, 36]} For example, in 1993, Dartevelle et al presented their experience with an anterior transcervical thoracic approach that permitted greater exposure and control of the vascular structures of the thoracic inlet, which facilitated resection in cases in which vascular structures were invaded.^[37]

Patients with superior sulcus pulmonary carcinoma should be considered for surgery after appropriate diagnostic evaluation. The ideal candidate has a carcinoma restricted to the chest with T3N0M0 staging. A rare exception is made for a right upper-lobe lesion with intranodal mediastinal metastases and T3N2M0 staging. However, surgery alone is not the prevalent course of treatment.

Surgery is indicated in patients who have very localized early disease. The occasional inoperable patient with severe pain after radiation therapy may be selectively considered for palliative resection. Contraindications to surgery include the following:

• Extensive invasion of the neck, brachial plexus, or vertebrae
• Perinodal mediastinal extension
• Peripheral metastases

These include extrathoracic metastatic disease and positive mediastinal nodes. Complete upper and lower brachial plexus invasion is a relative contraindication, provided that complete surgical excision can be performed. Vertebral body involvement should not be a contraindication unless invasion of the cortex is confirmed.

In general, medical management plays only a secondary role in the treatment of lung cancers. In patients with disseminated lung cancer, medical treatment is required for palliation and treatment of symptoms arising from paraneoplastic syndromes.

Data indicate that the best survival rate is obtained with preoperative chemoradiotherapy followed by surgical resection in carefully selected patients.^{[31, 38, 39, 40, 41]} Preoperative radiotherapy followed by surgery is a reasonable alternative in some patients. Involvement of the subclavian vessels or the vertebral column is associated with poor survival.^[40] However, a few centers have obtained decent experience with better surgical approaches to these structures and have published reasonable survival rates after surgery.

In a study of 56 patients in stage IIB to IIIB who were treated with a trimodal approach (2-3 cycles of a platinum-based chemotherapy associated with radiotherapy (30–44 Gy) followed by surgical resection of eligible patients 2 to 4 weeks post-radiation), a 5-year survival rate of 38% was achieved.^[42]  

To date, no data describe appropriate treatment for patients with unresectable tumors who may be curable. However, extrapolation from the data for non-Pancoast stage III non–small-cell lung cancer (NSCLC) suggests that chemoradiotherapy is the best approach. In patients whose disease is believed incurable, radiotherapy offers good palliation of pain.

Ultrasound-guided cervical nerve roots ablation can be considered for patients with intractable neuropathic pain secondary to Pancoast tumor. Anecdotal reports have described excellent pain relief as well as improvement in quality of sleep with this technique.

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Preoperative Evaluation

Patients with poor respiratory function and ischemic coronary artery disease need a proper workup before undergoing surgical therapy. Heart failure, recent myocardial infarction, and unstable angina are contraindications for surgery. Although many patients are elderly (the age group with the highest risk of complications), age alone is relatively unimportant if the patient is in otherwise good health.

Most of the postoperative complications that follow lung resection are cardiopulmonary (eg, myocardial ischemia, pulmonary embolism [PE], and respiratory failure). To avoid these complications, patients selected for surgery are required to undergo an evaluation of pulmonary function. High-risk patients benefit from supervised pulmonary rehabilitation accompanied by bronchodilator therapy.

Prophylactic heparin and antiembolic stockings are used in all patients. Preoperative nutritional status is carefully assessed in all patients because a low albumin level has been correlated with a higher morbidity.

All patients are encouraged to stop smoking at least 2 weeks before surgery. Preoperative assessment of cardiac risk factors is critical in evaluating candidacy for lung resection. Perioperative cardiac complications can be reduced preoperatively in patients at high risk by instituting better perioperative monitoring, performing a lesser procedure, or achieving medical optimization. Consider preoperative angioplasty or coronary bypass in all patients with significant coronary disease.

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Preoperative Chemoradiotherapy

In patients with a Pancoast tumor, a multimodality approach involving chemoradiotherapy and surgical resection seems to be optimal, provided that appropriate staging has been conducted. Patients with central T4 tumors that do not have mediastinal node involvement are uncommon. Such patients, however, seem to benefit from resection as part of the treatment as opposed to chemoradiotherapy alone when carefully staged and selected.

Currently, in accordance with the findings of the trial conducted by Rusch et al, most centers use cisplatin-based chemotherapy with etoposide and concurrent radiotherapy as neoadjuvant treatment, followed by surgical resection, as the standard of care for this group of patients.^[36] One cautionary note is that this trial mandated a negative mediastinoscopy result. The preoperative radiotherapy dose was 45 Gy in 25 fractions.

Radiotherapy

Radiation therapy is used as the sole treatment only for patients with unresectable tumors or for those who are not surgical candidates. It provides excellent pain relief, but no long-term survival occurs if the primary tumor is not controlled. The most common site of recurrence after resection is the central nervous system (CNS), especially if the primary tumor is an adenocarcinoma or large cell cancer. In these situations, prophylactic cerebral radiotherapy should be administered if local control has been achieved.

Previously, superior sulcus tumors were considered inoperable and were not often successfully palliated with radiation therapy alone. The best results seem to occur when the tumor and the localized adjacent area, including the superior mediastinal nodes, are preoperatively treated with 30-40 Gy of radiation administered over 2-3 weeks. The radiation field includes the primary tumor, adjacent mediastinum, and ipsilateral clavicular area. The purpose of the preoperative irradiation is to shrink the tumor and to temporarily block lymphatic spread.

Preoperative treatment with more than 40 Gy may lead to poor healing after surgery. An interval of 2-4 weeks after radiation therapy allows the radiation to have maximal effect. After 4 weeks, all patients are reassessed for surgery. If no distant disease spread has occurred, then surgery is offered. The tumor is then resected en bloc with the chest wall.

The presence of Horner syndrome or ipsilateral supraclavicular node involvement is not an absolute contraindication for combined preoperative radiation and surgery. In current practice, interstitial implantation of radioisotopes (brachytherapy) is performed in association with external radiation therapy.

Clinical studies demonstrate that preoperative irradiation in doses not sufficient to cause gross regression of the tumor is still beneficial, as it decreases local recurrences, prevents the growth of disseminated tumor cells, and increases survival compared with irradiation or surgery alone. Studies in selected patients have shown complete eradication of local growth, pain relief, and improved survival rates.

Whereas preoperative irradiation followed by complete en bloc resection represented an advance over previous treatment paradigms,^[43] the high frequency of local recurrence despite aggressive measures, coupled with the eventual development of distant disease and death, prompt continued exploration of novel approaches.

Some evidence indicates that a multidisciplinary approach using neoadjuvant chemotherapy and radiation (see below) may improve resectability. However, such an approach is also associated with increased incidence of postoperative distress syndrome.^[44]

Chemotherapy

The introduction of chemotherapy into the treatment plan, along with the development of newer modes of radiation therapy, brings the possibility of additional progress. Because Pancoast tumors are an uncommon subset of lung cancer, the number of cases has been insufficient to justify conclusions; however, further approaches to the general treatment of patients with regionally advanced disease (T3, chest wall invasion) are undergoing evaluation with chemotherapy, both with and without radiation therapy.

Data indicate that traditional treatment of Pancoast tumors with local approaches (surgery, radiotherapy, or a combination thereof) yields poor outcomes because of the high recurrence rate and the lack of systemic control. A trimodality treatment approach may improve local control and even survival.

There is evidence to suggest that induction chemotherapy combined with hyperfractionated accelerated radiotherapy before surgery may be effective in improving long-term survival and lowering recurrence rates. An empirical approach involving preoperative chemotherapy and radiation followed by surgical resection is being used in some centers, but no standardized protocols are available at present.

Several early trials demonstrated survival benefits in small groups of patients (not Pancoast patients) with locally advanced lung cancer treated with preoperative chemotherapy.^{[45, 46]} The largest study of this kind, reported by Albain et al, reported complete pathologic responses in 21% of surgical patients after preoperative concurrent chemotherapy and radiation therapy.^[47] The optimal chemotherapeutic regimen has not yet been identified, and newer agents may improve responses.^[48]

Although present-day management of Pancoast syndrome is largely based on the published retrospective experience of large single institutions, 2 prospective multicenter phase 2 studies that used a trimodality approach of induction concurrent chemoradiotherapy followed by surgery (followed by 2 additional cycles of adjuvant chemotherapy in 1 study), reported 5-year survival rates of 44-56%. These studies support the idea that a trimodality approach may be the ideal approach in the management of Pancoast tumors.^[49]

A lung intergroup trial (Southwest Oncology Group 0220) using induction therapy with cisplatin, etoposide, and radiotherapy with 45 Gy, followed by resection (if possible) and postoperative docetaxel, reported 5-year survival rates increasing to 44-56%, suggesting that this approach could be considered a new standard of care in the management of Pancoast tumors.

In various series, irrespective of local control of the tumor, a considerable number of patients died of distant metastases rather than of local disease. The microscopic presence of distant metastatic disease is not presently discernible by available conventional screening methods, which suggests that more potent chemotherapy might be necessary to control the disease.^[50]

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Surgical Resection

In many centers, the current practice is to individualize a treatment plan for each patient. Frequently, treatment decisions are made by a multidisciplinary thoracic oncology group with attention to adverse prognostic factors.

All patients with Pancoast tumors that are directly invading the parietal pleura and chest wall should undergo surgery, provided that the following conditions are satisfied:

• No distant metastases are present
• The patient’s cardiopulmonary status allows surgery
• No preoperative evidence of extensive mediastinal adenopathy is present

Involvement of mediastinal nodes is always associated with poor outcome after resection. At the time of surgery, a complete resection of all involved structures is recommended.

In most patients, the surgical treatment of choice is complete removal of the tumor by en bloc chest wall resection combined with lobectomy and node staging.^[19] Depending upon the extent of local invasion, surgical treatment may require resection of the paravertebral sympathetic chain, stellate ganglion, lower trunks of the brachial plexus, subclavian artery, or portions of the thoracic vertebrae. For tumors that invade the brachial plexus, the spine, or both, a combined thoracic-neurosurgical approach is warranted.

Some patients may have apical tumors that are not attached to the chest wall but for which computed tomography (CT) findings are inconclusive. In such cases, evidence suggests that thoracoscopy can be used to assess for chest wall invasion. With this strategy, unnecessary neoadjuvant treatment and futile thoracotomy may be avoided.^[51]

Video-assisted thoracic surgery (VATS) is increasingly used in the management of Pancoast tumors. By starting with thoracoscopy, the surgeon can assess for pleural dissemination and precisely define the tumor location as well as the extent of thoracic wall resection needed. Thus, VATS can reduce the magnitude of the operation, either by sparing the patient a useless thoracotomy or by optimizing the site of the thoracotomy; it may obviate rib retractor use and so minimize postoperative pain and post-thoracotomy syndrome.^{[52, 53, 54]}

Radiation and chemotherapy may benefit local and systemic control by addressing individual adverse findings. In many centers, neoadjuvant or induction chemoradiotherapy is administered to patients with potentially resectable tumors (see above). Important factors include T category, nodal status, presence of Horner syndrome, and completeness of resection.^{[19, 20, 21, 22, 23, 25]} Surgery is generally undertaken 2-4 weeks after the completion of radiation therapy.

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Technical approaches

A Pancoast tumor can be approached from either an anterior or a posterior incision. With the posterior approach, the incision is made along the contour of the scapula, and the pleural cavity is entered at the third or fourth intercostal space. Dissection from below prevents injury to the subclavian vessels and the brachial plexus.

Before any resection, the degree of tumor invasion must be assessed. The surgical technique for resection of a superior sulcus tumor is an extended en-bloc resection of the chest wall, including posterior portions of the first 3 ribs, part of the upper thoracic vertebrae (including the transverse process), the intercostal nerves, the lower trunk of the brachial plexus, the stellate ganglion, and a portion of the dorsal sympathetic ganglion, together with the involved lung portion. Determinants of unresectability include the following:

• Involvement of the subclavian artery
• Involvement of the vertebral body with or without cord compression
• Widespread invasion of the brachial plexus

The other approach to a Pancoast tumor is an anterior transcervical approach.^[37] Most authorities believe that injury to the subclavian vessels and the brachial plexus is much less common with this incision.

With the anterior transcervical approach, exposure of the jugular and subclavian veins is facilitated, and the thoracic duct is easily identified. Assessment of tumor invasion of the subclavian vessels is readily accomplished, and reconstruction of these vessels is easier. The anterior incision is not recommended for tumors that invade the posterior aspects of the ribs and their transverse processes, the stellate ganglion and sympathetic chain, and the vertebral bodies.

After the procedure is completed, 2 large pleural tubes are placed for drainage, one at the apex of the chest to drain any residual air and the other in the posterior gutter to drain fluid. Fix all drainage tubes to the skin site with a suture.

Surgical principles for curative resection of a Pancoast tumor can be summarized as follows:

• Excise the entire first rib and posterior segments of the second and third ribs
• Excise corresponding thoracic nerve roots up to the intervertebral foramen
• Excise portions of the upper thoracic vertebrae, including the transverse process if necessary
• Excise the lower trunk of the brachial plexus
• Excise part of the stellate ganglion and the thoracic sympathetic chain
• The lung resection can be either a wedge resection or a lobectomy
• Radical mediastinal lymph node dissection can be performed

Patients are cared for in the intensive care unit (ICU) and then extubated. Routine care of the chest tubes is maintained. Mortality from surgical resection of a Pancoast tumor ranges from 2% to 5%. After arrival in the ICU, vital signs are monitored every 15-30 minutes until the patient is stable. Urinary output, chest tube drainage, and temperature are monitored hourly. Daily chest radiographs are obtained until the drainage tubes are removed.

• References

Postoperative Radiotherapy

The adjuvant role for postoperative radiotherapy in superior sulcus tumors is undetermined. Radiotherapy is not indicated for patients who undergo complete resection and have no nodal metastasis. Yet, in the past, many people were treated with postoperative radiotherapy in response to an incomplete resection with residual disease. To date, postoperative radiotherapy has not improved survival in patients with lung cancer who underwent complete surgical resection without gross or microscopic residual tumor.

Some retrospective studies suggested that postoperative radiotherapy was beneficial for patients with nodal disease; however, several oncology trials found no survival benefit in patients who underwent complete resection. Postoperative radiotherapy does decrease the frequency of local (intrathoracic) recurrence.

Postoperative radiotherapy following immediate operation and brachytherapy has been as effective as preoperative radiation therapy and brachytherapy in achieving complete resection, locoregional control, and, ultimately, cure. No studies document the usefulness of chemotherapy in the treatment of this disease.

Surgical Complications

The morbidity arising from the operation is solely caused by the extent of chest wall and lung resection.

Atelectasis is very common with this operation and requires aggressive pulmonary toilet, incentive spirometry, and early ambulation. An adjunct to the treatment of atelectasis is bronchoscopy, which is frequently required to suction out mucous plugs and to drain secretions.

Almost all patients have severe chest wall pain, and epidural anesthesia is highly recommended. Patients who do not undergo thoracic epidural anesthesia usually report significant pain and require continuous narcotics, either intravenously or in patch form.

Cerebrospinal fluid (CSF) leaks occur but are rare; they usually subside with pleural drainage. If a CSF leak occurs in the presence of a pneumothorax, the air may enter the spinal cord and result in meningitis, which manifests as a severe headache. If the CSF leak persists, an exploratory thoracotomy is performed, and a muscle flap is used to close the area.

Most air leaks subside within a few days, and the drainage tubes are removed.

Permanent neurologic deficits are rare. They usually result from resection of the lower trunk of the brachial plexus, but they are not incapacitating. Horner syndrome may occur from resection of the stellate ganglion and the root of C8. Deficits are usually temporary, lasting a few months. To prevent the disabling symptoms from resection of the brachial plexus, some studies indicate that neurolysis and preservation of the brachial plexus by a neurosurgeon may improve surgical outcome and postoperative symptoms.^[55]

The 5-year postoperative survival rate is approximately 30%. Intraoperative brachytherapy has had no influence on locoregional recurrence or survival in patients with completely resected tumors. In the presence of positive mediastinal lymph nodes, the median survival rate is less than 9 months.

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Palliative Procedures

Poor local control of a Pancoast tumor leads to significant intractable pain. The pain is caused by tumor invasion of the brachial plexus and nerve root compression in the intervertebral foramina, which is difficult to control.

Palliative surgery does not always provide relief from pain. However, when epidural compression is imminent, surgical maneuvers that alleviate this compression are of value. Techniques employed to interrupt pain pathways include the following:

• Cervical cordotomy
• Selective posterior rhizotomy
• Stereotactic thalamotomy
• Commissural myelotomy

Occasionally, radiotherapy is required for pain control.^[31] Radiation in doses of 40-60 Gy is administered over a period of 3 weeks, eliciting relief of pain in 90% of patients and occasionally reversing hoarseness and Horner syndrome. However, most patients die within 2 years. The most common site of metastatic disease is the brain.

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Medication Summary

The goals of pharmacotherapy for Pancoast tumor are to induce remission, reduce morbidity, and prevent complications. Chemotherapy is typically part of multimodal treatment that also includes surgery and radiation therapy.

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Cisplatin (Platinol)

• Dosing, Interactions, etc.

Clinical Context:  Cisplatin is an alkylating agent that causes intrastrand and interstrand cross-linking of DNA, leading to strand breakage. It has broad range of antitumor activity and forms the backbone of currently available approved combination chemotherapy regimens for SCLC and non-SCLC (NSCLC) that cause Pancoast syndrome.

Cisplatin is administered by intravenous infusion in isotonic sodium chloride solution (0.9%) or sodium chloride and glucose. The manufacturers recommend that higher doses be administered in 2 L of chloride-containing infusion fluid over at least 1-2 hours and that an infusion time of 6-8 hours may further reduce toxicity. In practice, volumes of less than 2 L have been used in expert centers.

To aid diuresis and protect the kidneys, 37.5 g of mannitol (eg, 375 mL [10%]) is usually added to the infusion, or is infused separately, immediately before cisplatin. To initiate diuresis, the patient is usually hydrated by the infusion of 1-2 L of a suitable fluid over several hours before the administration of cisplatin. Adequate hydration must also be maintained for up to 24 hours after a dose. Renal, hematologic, auditory, and neurologic function should be monitored during therapy and administration adjusted accordingly.

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Etoposide (Toposar)

• Dosing, Interactions, etc.

Clinical Context:  Etoposide is a semisynthetic derivative of podophyllotoxin with antineoplastic properties; it interferes with the function of topoisomerase II, thus inhibiting DNA synthesis, and is most active against cells in the late S and G(2) phases of the cell cycle.

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Class Summary

Antineoplastic agents inhibit cell growth and proliferation. They are used to treat the following conditions:

- Head, neck, breast, testicular, and ovarian cancer

- Hodgkin and non-Hodgkin lymphoma

- Neuroblastoma

- Sarcomas

- Bladder, gastric, lung, esophageal, cervical, and prostate cancer

- Myeloma

- Melanoma

- Mesothelioma

- Small cell lung cancer (SCLC)

- Osteosarcoma

- Acute nonlymphoblastic leukemia

- Hepatoma

- Rhabdomyosarcoma, mycosis fungoides, uterine carcinoma, and histiocytosis

- Gestational trophoblastic disease

- Ewing sarcoma, Kaposi sarcoma, Wilms tumor, and brain tumors

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