Lung cancer



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STAGE GROUPING

Occult carcinoma

TX, N0, M0

Stage 0

Tis, N0, M0

Stage IA

T1, N0, M0

Stage IB

T2, N0, M0

Stage IIA

T1, N1, M0

Stage IIB

T2, N1,M0
T3, N0, M0

Stage IIIA

T3, N1,M0

T1-3, N2,M0

Stage IIIB

T1-3, N3, M0
T4, N0-3, M0

Stage IV

Any T, Any N, M1

To define the T characteristics of a lesion, chest roentgenography and fiberoptic bronchoscopy are required. Occasionally, CT or MRI can be useful in anatomically defining T3 or T4 lesions.

To define the N characteristics of a lesion, some combination of chest roentgenography, CT or MRI scanning, transbronchial needle aspiration (TBNA), or mediastinoscopy is required.

There is now general agreement that nodal enlargement identified by CT requires tissue confirmation of metastasis by mediastinoscopy or alternate biopsy technique, except when gross mediastinal invasion by tumor (T4) is present. A patient should not be denied potentially curative surgery based solely on radiographic criteria. Emphasizing this point, a recent study demonstrated that 37% of lymph nodes measuring 2-4 cm in short-axis diameter on CT did not contain metastases at the time of surgery. CT scanning is also useful in identifying the site(s) of mediastinal node enlargement, especially those that may not be accessible to standard mediastinoscopy (aortopulmonary nodes, anterior mediastinal nodes, paraesophageal nodes, and inferior pulmonary ligament nodes). Also, extension of the CT examination to include the adrenal glands and liver may often detect the presence of occult metastatic disease. The role of MRI scanning remains limited due to its poorer spatial resolution compared to CT, its expense, and its limited ability to detect calcification.

To define the M characteristics of a lesion, the triad of history, physical examination, and an admission chemistry panel, including liver function tests, is recommended. Unless an abnormality is identified by that triad, routine screening by means of multiple organ scans is not recommended. In the case of radioisotopic liver and bone scans, the incidence of false-positive scans is appreciable, necessitating an invasive and costly workup with low yield. Although the evidence remains somewhat conflicting, certain authors believe that the performance of a head CT scan in asymptomatic patients with adenocarcinoma of the lung does represent a prudent preoperative examination.

Combining the TNM elements results in subsets that can be further grouped to depict stages or extent of disease. Stage I includes only patients with the best prognostic expectations, those with T1 or T2 tumors and no evidence of metastasis. Stage II disease includes patients with primary tumor classification of T1 or T2 and metastasis to the intrapulmonary (including hilar) lymph nodes. Stage IIIA disease designates those patients with extrapulmonary extension of the primary tumor or ipsilateral mediastinal lymph node metastasis or both. Stage IIIB includes patients with more extensive extrapulmonary involvement than in the potentially operable stage IIIA group, those having malignant pleural effusion, and those with metastasis to the scalene, supraclavicular, or contralateral mediastinal or hilar lymph nodes. Stage IV disease is confined to those patients with metastasis to distant sites.


ATYPICAL FORMS

The mediastinal form of a LC is characterized by defeat of mediastinal lymph nodes. The initial tumor is in bronchi and gives roughly growing metastases in mediastinum, considerably outstripping growth of an initial tumor. The clinical picture is characteristic by signs of compression of a superior vena cava: cyanosis and edema of head and neck, phlebectasia of neck and chest. At a palpation of a neck the augmentation of supraclavicular lymph nodes owing to their metastatic defeat is frequently determined.

Miliar carcinosis develops in connection with a rough innidiation of a tumor by the lymphogenous or hematogenous way in affected or opposite lung. The picture reminds lung tumoral multilocular diffusion by small "millet-similar" nodules. It is not possible to find the primary tumor in lung.

The cardial form of a LC is characteristic by the signs reminding ischemic desease of the heart. Patients address to the theraputist or to the cardiologist and long time they are treated with the diagnosis "ischemic desease of the heart". The reason of such manifestation of a LC frequently is the tumor invasion in a pericardium. Especially at left-sided localization in the lower lobe of left lung the shadow of a tumor long time is near with a cardiac shadow, and only additional methods of a X-ray examination allow to determine it.

Osteal, cerebral, hepatic forms etc. are frequent variants of atypical picture of a LC. Each of the listed forms is characterized by dominant clinic of metastatic defeat of one of the specified organs or systems with the minimal displays of an initial tumor of a bronchus.
COMPLICATED LUNG CANCER

The compression of vena cava superior (cava-syndrome) develops as a result of a compression of this vessel directly by a tumor of right lung or by metastases of a cancer in a mediastinum. Vena cava superior – an unique vessel by which the blood comes back to heart from a head, neck, top extremities and the upper half of trunk. Compression or an invasion of this vein by a tumor may be cause of a decompensation when the blood from the specified departments of a body may not return to the right auricle, and venous stagnation develops. It is shown by various objective and subjective attributes: cyanosis of seen mucosas and skin of the face; edema of face or top extremities, expansion of hypodermic veins of neck and anterior thoracic wall; the venous network reminds a head of a jellyfish (“Caput medusae”); hum and gravity in a head are marked.

The esophago-bronchial fistula concerns to infrequent, but to the most severe complications of a LC. The pathological connection between bronchi and esophagus is formed owing to disintegration or a radial destruction of a LC. Clinically formation of an esophago-bronchial fistula is shown by fits of severe coughing during eating or drinking. At a X-ray inspection of an esophagus with use of a contrast agent its passage from an esophagus to a bronchial tree is taped. The condition of the patient is quickly worsened in connection with development of aspirational pneumonias. The basic actions should be directed on stop of nutrition passage into bronchi from esophagus and struggle against a pneumonia.

The profuse pulmonary bleeding at a LC comes as a result of disintegration of a tumor and arrosion of branches of bronchial or pulmonary vessels. The pulmonary bleeding is characterized by the fits of coughing, accompanying with discharging from a mouth of a scarlet foamy blood. Sometimes patients choke, not having time to expectorate blood. Paleness of skin, cold sweat, syncope, tachycardia, arterial hypotension are marked. Plural atelectasises and the centers of aspirational pneumonias develop in lung.

The lung atelectasis develops owing to an obturation by a tumor of a main bronchus. It is accompanied by a short wind, chest pain, tachycardia. Radiologically the massive blackout (lung without air) and shift of a mediastinum to a side of an atelectasis are taped (Fig. 23).

a b


Fig. 23. a) collapse of the left lung with mediastinal shift and a right middle zone nodule (arrow); b) perihilar low attenuation adenocarcinoma (arrows) with distal enhancing collapsed lung in same patient.
TREATMENT OF THE LUNG CANCER

Surgery and radiotherapy have been used independently to obtain local control of the primary tumor and regional lymphatic drainage. Until recently, chemotherapy had been used in an attempt to prolong symptom-free life in patients with metastatic disease. In the past 20 years, however, combined-modality therapies have become much more prevalent and have spurred intensive investigation. All three modalities are now used as primary therapy and, in combination, have been employed to improve disease-free intervals and ultimate survival.


SURGICAL TREATMENT OF THE LUNG CANCER

Unique method of radical treatment of LC is surgical. Once histologic proof of lung carcinoma is obtained, resectability is determined by the histopathology and extent of the tumor and by operability according to the overall medical condition of the patient. Age and mental illness per se are not factors in deciding operability. Approximately 50 percent of patients with NSCLC are potentially operable. About 50 percent of tumors in operable patients are resectable (25% of all patients) and, approximately 50 percent of patients with resectable tumors survive 5 years (12% of all patients, or 25% of operable patients).



Signs of unresectable lung cancer.

a. Distant metastases, including metastases to the opposite lung.

b. Persistent pleural effusion, with or without malignant cells (a parapneumonic effusion that clears and may permit subsequent resection).

c. Superior vena cava obstruction.

d. Involvement of the following structures:

1) Supraclavicular or neck lymph nodes (proved histologically).

2) Contralateral mediastinal lymph nodes (proved histologically).

3) Recurrent laryngeal nerve.

4) Tracheal wall.

Cardiac status. The presence of uncontrolled cardiac failure, uncontrolled arrhythmia, or a recent myocardial infarction (within 3-6 months) makes the patient inoperable.

Pulmonary status. The patient's ability to tolerate resection of part or all of a lung must be determined. The presence of pulmonary hypertension or of abnormalities on certain pulmonary function tests makes the patient inoperable.

Clinical observation. Any patient who can walk up a flight of stairs without stopping and without severe dyspnea is likely to tolerate a pneumonectomy.

Routine pulmonary function tests. Arterial blood gases and spirometry should be obtained on all patients before surgery. Pulmonary function tests must be interpreted in the light of optimal pulmonary toilet and patient cooperation. The patient with test abnormalities should be considered for therapy with bronchodilators, antibiotics, chest percussion, and postural drainage before inoperability is concluded. The following results suggest inoperability:

1) Forced vital capacity (FVC) less than 40 percent of predicted value, or

2) Maximum voluntary ventilation (MVV) less than 50 percent of predicted value, or

3) Forced expired volume at one second (FEV1.0) < or equal to 1.0 L

Clinical stage grouping defines tumor spread and the potential for curative resection, thereby determining which patients should or should not be referred for surgery. Surgical decisions related to staging that are based on T or M characteristics are clear-cut:

1) all operable patients with stage I or II should have definitive surgery;

2) all patients with stage IIIB or IV disease have nonsurgical disease.

With respect to N characteristics in stage IIIA disease, the issue is not as clear. Patients with N2 disease discovered at thoracotomy following a negative mediastinoscopy have been demonstrated to have an improved survivorship compared to those patients in whom N2 disease is discovered at mediastinoscopy. Specific characteristics of the node or nodes other than their location affect the potential for resectability:

1. Number of nodes: Prognosis has been shown to be better for single-level nodal metastases than for multilevel nodal involvement.

2. Character of nodal involvement: A number of reports have suggested that prognosis is related to whether the tumor is contained within the node (intranodal disease) or has spread beyond the nodal capsule (perinodal disease).

3. Specific location of nodal involvement: Although still a subject of controversy, several studies have reported that the survival rate of patients with subcarinal lymph node metastases was lower than the survival rate of patients with metastases to lymph nodes in other mediastinal locations. The data underscore the need for a uniform mapping system of specific nodal locations to ensure clear and precise definition of the findings at thoracotomy so that these findings can be correlated with outcome.

The basic standard operations are: lobectomy, pneumonectomy, extended pneumonectomy (removing of a mediastinal fat with lymph nodes), combined pneumonectomy – removing of a lung with a pericardium site, diaphragm site or thoracic wall site.

Recent years bronchoplastic operations are more often carried out allowing as much as possible to keep a respiratory lung volume. Removing of the upper lobe with a circular resection of a main bronchus is the most frequent one.

Surgical resection offers the only definitive means of therapy by which non-small-cell lung cancer (NSCLC) can be cured. Unfortunately, less than 30% of patients with newly diagnosed lung cancer fall into a favorable survival group at the time of diagnosis, thereby accounting for the barely perceptible increase in 5-year survival rates of 50-60% in stage I disease, 30-40% in stage II disease, and 10-20% in stage IIIA disease. The most adverse forecast have undifferentiated cancers (small cell and giant cellular). Improved patient selection and advances in preoperative management, anesthetic techniques, and postoperative care have led to a dramatic decline in mortality rates for pulmonary surgery. Data from the Lung Cancer Study Group have demonstrated mortality rates of 6.2% for pneumonectomy, 2.9% for lobectomy, and 1.4% for lesser procedures.

General 5-year survival rates after surgical treatment of a LC makes about 30%. At treatment of patients in stage T1-2N0M0 it increases up to 80 %.


RADIOTHERAPY OF THE LUNG CANCER

Radiotherapy for the treatment of LC has experienced significant changes in a short time with respect to the evolution of appropriate patient selection, radiobiologic principles, technical innovation, imaging, and the use and integration of chemotherapy and surgery. Radiotherapy is applied as an independent method of treatment, and in a combination with a surgery or chemotherapy. The most widespread is application of gamma-therapy with a radioactive source 60Co (a radiation energy 1,25 МeV).

Since 1960th high-energy radiations of linear and cyclic particles accelerators are applied for treatment of malignant tumors. More favourable spatial distribution of high-energy radiation (5-45 MeV) is especially shown at deeply posed neoplasms, including a LC.

Radical radiootherapy provides reception of long and proof effect as a result of destruction of all tumor in irradiated volume when at a palliative irradiation there is only partial destruction of tumor. The volume of the tissues, exposed to radical radial influence, should cover a seen initial tumor, probable lymphogenous metastases: bronchopulmonary, hilar, upper and lower tracheobronchial, paratracheal lymph nodes. The radical program of an irradiation at undifferentiated small cell forms of a LC provides a preventive irradiation of supraclavicular areas with the purpose of destruction of subclinical metastases. The cooperative focal dose necessary for destruction of an initial tumor varies from 50 up to 80 Gy and depends on histological structure of a tumor.

Radiotherapy of a peripherial LC has own features. In a field of an irradiation are included a shadow of a tumor, radiological "path" to a lung hilar (which displays infiltration of a peribronchial and perivascular tissue by tumor), zones of regional lymph nodes.

In case of mediastinal form of a LC, and also in any other form with a massive innidiation in lymph nodes of a mediastinum with a compression of the large veins causing development of the mediastinal compressional syndrome, radial treatment is the best one.

Postoperative radiotherapy had been standard treatment after surgical resection of N2 disease. Its ability in moderate doses of 40–55 Gy to eradicate microscopic residual disease and reduce local recurrent rates is well established.

Palliative radiotherapy can be effective at relieving local symptoms of lung cancer. Quality of life data from the British MRC randomized trials of 1 and 2 fractions of treatment versus more conventional treatment consisting of 10 or 13 fractions have shown improvement in local symptoms, including chest pain, cough, and breathlessness, in more than 50% of cases, with 90% of those having hemoptysis being controlled. These showed that shorter schedules using one or two fractions of radiotherapy are just as effective at obtaining relief of local symptoms without detriment to survival time or an increase in toxicity relative to higher dose, short courses. The MRC studies (1991, 1992, and 1996) also included careful assessment of quality of life with daily diary cards, confirming good durability of palliation and minimal toxicity.

Smaller doses of radiotherapy can be used if delivered directly to the airway (endobronchial brachytherapy) and are particularly useful in those patients who have received close to the maximum safe dose of external beam radiotherapy, and in those with tumor localized to within or close to the airway lumen. Radical radiotherapy can also be delivered in this way. Endobronchial brachytherapy has been used in one form or another for at least 80 years with radium needles and cobalt pearls used commonly in 1960s and 1970s to destroy local tumor in the upper airways. Iridium has now become the standard mode of delivery of irradiation via a catheter placed in the airway through a flexible bronchoscope under radiographic control. Iridium provides small-volume irradiation with a steep decrease in radiation isodoses within a few millimeters of the source axis. The target dose depends on the intent, with 10–15 Gy in 10 mm for palliation, and 20–25 Gy if cure is intended for a localized small lesion. The response to brachytherapy is slow, over 10 to 20 days, and appears to be safe in doses of 5 Gy over two to four sessions, even if radical radiotherapy has been given earlier. In fact, the commonest setting for brachytherapy is for local relapse after previous radical radiotherapy.

The addition of iridium-192 brachytherapy has been demonstrated to prolong the duration of palliation substantially, although such complications as hemorrhage or airway fistulization with the esophagus or major vessels have been reported in 10-15% of treated patients.

The role of laser therapy in endobronchial carcinoma is evolving. Palliation of airway obstruction can be achieved when obstructing lesions involve the trachea and mainstem bronchi. Treatment appears most successful when the lesions are short in length, when the distal bronchi are free of tumor, and when there is functioning lung tissue distal to the obstruction.

One nonsurgical method of treating early lung cancers is by endobronchial photodynamic therapy (PDT) under local anesthesia and sedation. PDT is approved for the endobronchial treatment of microinvasive NSCLC and for palliation in patients with obstructing tumors. A mixture of different porphyrin-based oligomers (such as Photofrin [porfimer sodium]) is injected intravenously, with care not to extravasate. The drug is cleared in 72 hours, but is retained for up to 30 days in tumors, skin, liver, and spleen. After 48 hours light with a wavelength of 630 nm is shone from a laser onto the tumor and the resulting phototoxic reaction destroys tumor to a depth of 5 to 10 mm.

The light is delivered through a cylindrical diffuser fiber that is passed through the working channel of the flexible bronchoscope and the tip is then embedded into the lesion. The bronchoscopy should be repeated at 48 hours to clear debris and secretions and prevent compromise of the airway (a particular problem when treating tracheal lesions, and those requiring high energy levels).

Another complication of PDT is skin photosensitivity. Patients are kept in special hospital rooms and are given advice before discharge such as to avoid even normal daylight for 4–6 weeks after the injection. Care should be taken when using pulse oximeters, which have caused severe finger-tip burns for monitoring patients during the procedure.

PDT has been used to treat early lung cancers (less than 10 mm in diameter) with a cure rate of more than 75%. There is some early evidence that EBUS can be used to select for tumors in the large airways that are sufficiently localized (i.e., have not extended beyond the airway cartilage) to be treated by PDT with curative intent, as an alternative to surgery. PDT has also been assessed for use as a palliative treatment and has been shown to perform as well as other modalities, in particular the Nd:YAG laser, in relieving endobronchial obstruction by NSCLC. However, care must be taken as the time lag between treatment and tissue necrosis means that PDT is not suitable for emergency relief of obstruction, and in addition, obstruction may worsen because of the intense inflammatory response at 24–72 hours posttreatment, so that bronchoscopy and resuscitation equipment must be available.


CHEMOTHERAPY OF THE LUNG CANCER

For realization of drug treatment of a LC morphological confirmation of the diagnosis, establishment of histological type of a tumor, specification of prevalence of process in organs and tissues, an estimation of the general condition of the patient are necessary. Special value in chemotherapy of a LC has the histological type of a tumor, which defines character of chemotherapy, and also the forecast for effect of treatment and survival.

Chemotherapy has been evaluated as neoadjuvant and adjuvant treatment around surgery, neoadjuvant and adjuvant around radiotherapy, and as primary treatment for advanced inoperable disease.

Indications to chemotherapy of a LC:


  • Not removable surgically initial lung tumor.

  • Impossibility of application of radial treatment.

  • The plural remote lymphogenous metastases.

  • The specific pleuritis confirmed with cytologic exudate examination.

  • Progression of disease in various terms after operation.

  • Absence of the effect after radiotherapy.


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