Photodynamic therapy for patients with advanced non-small-cell carcinoma of the lung

Patients with advanced non-small-cell lung carcinoma (NSCLC) have poor prognoses and experience negative sequelae of disease. Patients often suffer from dyspnea and/or hemoptysis, with overall pulmonary compromise. Patients with advanced, inoperable disease have limited options for treatment. This study summarizes our early experience and findings using photodynamic therapy (PDT) as an effective modality in the palliation of hemoptysis, dyspnea, and physical airway obstruction in cases of inoperable lung cancer. A retrospective review was conducted for the first 10 patients diagnosed with stage III/IV obstructive NSCLC who underwent PDT at our institution. Endobronchial lesions were identified by bronchoscopy. Treatments were initiated 48 hours after intravenous injection of 2 mg/kg of the photosensitizing agent porfimer sodium (Photofrin, QLT PhotoTherapeutics, Vancouver, BC). The porfimer sodium was then activated by illumination with a 630 nm wavelength light using a Coherent argon ion laser through a flexible bronchoscope. Repeated bronchoscopies were performed 1-3 days following initial PDT for evaluation and airway debridement. In 8 cases, a second treatment of PDT was administered within 72 hours of the first injection. One patient received a third treatment several months later. Three patients also received endobronchial stents after PDT. Overall, all 10 patients responded to PDT. Physical airway obstruction was reduced in all patients, with a noted improvement in bronchoscopic luminal diameter. Acute hemoptysis resolved in all 7 symptomatic patients. Median survival was 5.5 months post-PDT, while median survival postdiagnosis was 10.5 months. Three patients are alive at the time of this review at 5-21 months following therapy. Patients with unresectable late-stage NSCLC have few options for treatment. Our early experience with PDT indicates effective relief of hemoptysis, dyspnea, and airway obstruction and improves their quality of life.     

High-dose-rate endobronchial brachytherapy for recurrent airway obstruction from hyperplastic granulation tissue

PURPOSE: Benign endobronchial granulation tissue causes airway obstruction in up to 20% of patients after lung transplantation or stent placement. High-dose-rate endobronchial brachytherapy (HDR-EB) has been successful in some cases refractory to standard bronchoscopic interventions. METHODS AND MATERIALS: Between September 2004 and May 2005, 8 patients with refractory benign airway obstruction were treated with HDR-EB, using one to two fractions of Ir-192 prescribed to 7.1 Gy at a radius of 1 cm. Charts were retrospectively reviewed to evaluate subjective clinical response, forced expiratory volume in 1 second (FEV(1)), and frequency of therapeutic bronchoscopies over 6-month periods before and after HDR-EB. RESULTS: The median follow-up was 14.6 months, and median survival was 10.5 months. The mean number of bronchoscopic interventions improved from 3.1 procedures in the 6-month pretreatment period to 1.8 after HDR-EB. Mean FEV(1) improved from 36% predicted to 46% predicted. Six patients had a good-to-excellent subjective early response, but only one maintained this response beyond 6 months, and this was the only patient treated with HDR-EB within 24 h from the most recent bronchoscopic intervention. Five patients have expired from causes related to their chronic pulmonary disease, including one from hemoptysis resulting from a bronchoarterial fistula. CONCLUSION: High-dose-rate-EB may be an effective treatment for select patients with refractory hyperplastic granulation tissue causing recurrent airway stenosis. Performing HDR-EB within 24-48 h after excision of obstructive granulation tissue could further improve outcomes. Careful patient selection is important to maximize therapeutic benefit and minimize toxicity. The optimal patient population, dose, and timing of HDR-EB should be investigated prospectively.     

Endobronchial irradiation for malignant airway obstruction

An afterloading endobronchial irradiation (EBRT) technique using Iridium-192 (Ir-192), was piloted for malignant airway obstruction. Under bronchoscopic guidance, a catheter is threaded distal to the lesion. Orthogonal radiographs and computerized tomographic (CT) scans are obtained for dosimetry. Forty implants in 38 patients have been performed. Thirty-two patients had lung cancer; 23 had received prior irradiation and eight had prior chemotherapy. Eight patients underwent pre-endobronchial irradiation laser excision. Median implant duration was 50.5 hr; median dose at 1 and 2 cm from source center was 50 and 20 Gy, respectively. The procedure was well tolerated with four long-term complications (10.5%). Twelve of 38 patients are currently alive with a median survival of 5+ months and a range of 1 to 21+ months. Changes in performance status (PS), symptom resolution, radiographic demonstration of re-aeration of atelectatic lung, changes in pulmonary function (PFT), and post-endobronchial irradiation bronchoscopy were used to assess response. Seventy percent of the patients' remaining life was rendered symptom-free or improved. A 70% radiographic response was noted. Fourteen patients underwent post-endobronchial irradiation bronchoscopy with 12 complete responses. Endobronchial irradiation, therefore, appears to be a safe, effective technique to palliate malignant airway obstruction.     

Respiratory emergencies

Respiratory emergencies may originate from disease in the airways, thoracic vessels, and pulmonary parenchyma. Airway obstruction may be amenable to bronchoscopic therapies, including laser ablation photodynamic therapy (PDT) and stent placement. Asthma is common, but may be mimicked by endobronchial metastasis. Superior vena cava syndrome (SVCS) is seen most commonly with bronchogenic carcinoma and lymphoma. Emergent treatment need not precede tissue diagnosis in the absence of associated tracheal obstruction. Pulmonary embolism (PE) may now be diagnosed with spiral computed tomography (CT), but ventilation perfusion scintigraphy remains the first-line test. Parenchymal lung disease may result from infections, with neoplastic and iatrogenic etiologies. The incidence of Pneumocystis carinii pneumonia (PCP) is increasing among cancer patients, but it can be prevented by prophylaxis. Attempts to treat adult respiratory distress syndrome (ARDS) through modification of inflammatory mediators have been disappointing, and the prognosis remains poor.     

纤维支气管镜下大剂量腔内放疗治疗癌性支气管阻塞

目的　应用后装设备在纤维支气管镜引导下将192Ir导入支气管内进行腔内放疗,治疗癌性支气管阻塞。方法　常规纤维支气管镜检后,将施源器导管经活检孔导入病变部位,接后装机进行放疗,每次6～8Gy,每周1次,连续3周为1疗程。疗程结束后第1、4周复查。结果　胸部X线检查示:CR15例(23.08%),PR28例(43.08%),MR12例(18.46%),总有效率(CR+PR+MR)为84.62%。纤支镜检查示:CR25例(38.46%),PR28例(43.08%),MR9例(13.85%),总有效率为95.38%。结论　该方法对肺癌引起的支气管阻塞具有良好的再通效果,作用快,疗效好,副作用少。     

Long-term results of endobronchial brachytherapy: A curative treatment?

PURPOSE: To evaluate outcomes after high-dose-rate endobronchial brachytherapy (HDR-EBBT) for limited lung carcinoma. METHODS: A total of 106 patients with endobronchial lung cancer and not eligible for surgery or external beam radiotherapy, without nodal or visceral metastases, were treated with HDR-EBBT. They had developed disease relapse after surgery (n = 43) or external beam radiotherapy (n = 27) or had early lung cancer with respiratory insufficiency (n = 36). Treatment consisted of six fractions of 5 or 7 Gy, usually delivered 1 cm from the source. RESULTS: The complete histologic response rate, evaluated at 3 months after HDR-EBBT, was 59.4%. At 3 and 5 years, the local control, overall survival, and cause-specific survival rates were 60.3% and 51.6%, 47.4 and 24%, and 67.9 and 48.5%, respectively. Factors significantly associated with local failure were high tumor volume (tumor length >2 cm, bronchial obstruction >25%, tumor visibility on CT scan) and previous endoscopic treatment. Cause-specific survival, but not overall survival, was significantly associated with local control, probably because of the high rate of deaths not related to lung cancer. Five deaths were attributed to the HDR-EBBT procedure (two from fatal hemoptysis and three from bronchial necrosis). CONCLUSION: High-dose-rate-EBBT achieved a long-term cause-specific survival rate of 50% of the patients with localized endobronchial carcinoma and could be considered curative.     

Bronchoscopic intratumoral chemotherapy of lung cancer

Described in this review is a therapeutic procedure for localized chemotherapy of lung cancer by bronchoscopic intervention. This procedure involves the intratumoral injection of one or several conventional cytotoxic drugs directly into tumor tissue through a flexible bronchoscope by means of an ordinary needle-catheter, and is termed "endobronchial intratumoral chemotherapy" (EITC). Intratumoral (IT) chemotherapy should not be considered merely an ablation technique for treatment of endobronchial tumor bulk such as other ablative endoscopic procedures. EITC rather affords a significant specific chemotherapeutic effect on malignant cells through the localized action of cytotoxic drugs. Although superficially similar to ablative methods such as brachytherapy and photodynamic therapy, EITC provides the multiple benefits of rapid initial eradication of tumor burden inside the airway lumen plus intratumoral delivery of cytotoxic drugs as a loco-regional neoadjuvant therapeutic modality prior to irradiation or surgery. It is localized chemotherapy which differs from intravenous chemotherapy by the route of delivery and mode of action. The manifold advantages of the EITC intratumoral injection procedure include (1) precise delivery of cancer drugs to and within the tumor, (2) complete perfusion of the lesion, (3) dramatically higher intratumor drug concentrations than possible by systemic drug delivery, and (4) virtually none of the toxic side effects which normally occur with conventional systemic chemotherapy. In this comprehensive review of endobronchial intratumoral chemotherapy of lung cancer via bronchoscopic needle-catheter our objective is to describe the clinical procedure, the outcomes, and the advantages for this neoadjuvant therapeutic procedure.     

Photodynamic therapy in lung cancer

Photodynamic therapy (PDT) involves the use of photosensitizing agents that are selectively retained within tumor cells. The agents remain inactive until exposed to light of the proper wavelength. When activated by light, these compounds generate toxic oxygen radicals that result in tumor necrosis. In lung cancer, PDT can be used for both carcinoma in situ and for the treatment of unresectable disease with endobronchial obstruction. For patients with advanced disease, careful patient selection and integration of PDT with other interventional techniques are critical. Limited data suggest that PDT is comparable in efficacy to neodymium-yttrium-aluminum garnet (Nd-YAG) laser therapy, and some evidence indicates that it may be superior in terms of duration of response. For PDT to be used effectively, it should be integrated into a multimodality approach with chemotherapy and radiation. The optimal sequencing of these treatment modalities remains an area for further investigation.     

Prognostic variables in patients with hepatic metastases from colorectal cancer. Importance of medical assessment of liver involvement

Variation in response rates to chemotherapy and survival in patients with hepatic metastases from colorectal carcinoma may be due to patient selection factors. The prognostic importance of 13 factors were analyzed in 112 patients with only hepatic metastases, who were eligible for hepatic artery infusional chemotherapy. When individually analyzed, six factors were found to significantly (less than 0.001) affect survival: the percentage of tumor involvement of the liver, assessed medically or surgically; initial serum albumin and lactic dehydrogenase; initial Karnofsky performance status; and weight loss. Patients with less than or equal to 30% liver involvement had a median survival of 24 months versus 10 months if they had greater than 30% involvement. There was a highly significant agreement between medical and surgical assessment of liver involvement (P = 0.0001). When the variables affecting survival were studied together by multivariable analyses, the most important factor was the medical assessment of liver involvement accomplished by evaluation of radionuclide liver scan and CTT scans. The next two most important factors in the model were the ability of the patient to obtain a tumor response and the presence or absence of weight loss. Only one factor helped predict response to chemotherapy, the type of perfusion seen on a 99Technetium-macroaggregated albumin (MAA) arterial flow scan. Forty-five percent of patients with good perfusion had a partial response while 13% of patients with poor perfusion had a tumor response (P = 0.006). We recommend that future studies, dealing with patients who have hepatic metastases from colorectal carcinoma and are eligible for hepatic arterial infusion, document and stratify for the following factors: the percentage of liver involvement, the presence or absence of weight loss, and the type of perfusion seen on MAA scans.     

Diagnosis and significance of liver metastases in small cell carcinoma of the lung

One hundred fifty-seven consecutive patients with small cell lung cancer seen at the National Cancer Institute over a four-year period underwent a series of pretherapy liver staging procedures to determine optimal means of detection and prognostic implications of hepatic metastases. Liver evaluation included physical examination, liver function tests, and liver scan (radionuclide or computerized tomography [CT]), as well as percutaneous and/or peritoneoscopy-directed liver biopsy when possible (74%). Liver metastases were detected in 26% of patients. Peritoneoscopy was the most sensitive method of liver evaluation and increased the detection of liver metastases when done in a sequential fashion after percutaneous liver biopsy from 18 to a total of 27 patients. Of the noninvasive procedures, radionuclide and CT liver scan were the most accurate concurring with liver biopsy in 87% of patients but permitting correct discrimination of stage in excess of 96% of patients. The accuracy of this noninvasive procedure was enhanced by an algorithm combining the results of radionuclide liver scan with liver function tests to detect patients with high or low likelihood of liver involvement. The survival and response of patients with liver metastases was significantly worse than those without such metastases with no three-year disease-free survivors among patients with liver metastases.     

Pre-therapy CT scan showing peritoneal thickening from metastatic renal pelvis carcinoma patients

We investigated clinical significance of peritoneal thickening from metastatic renal pelvis based on pretherapy computed tomography (CT) scan findings. The criteria for inclusion were as follows: (1) pathology and CT scan confirmed metastatic renal pelvis carcinoma and (2) peritoneal thickening based on pre-therapy CT scan findings. We investigated the route of spread, gastrointestinal (GI) complications, and response to chemotherapy. A total of 68 cases were enrolled in this study, including seven patients with liver metastases and three with abdominal wall invasion. GI complications included obstruction in ten patients and bleeding in three. Response to chemotherapy demonstrated by reduced peritoneal thickening was noted in 24 patients. In conclusion. peritoneal thickening with clinical suspicion of peritoneal involvement can get indirect evidence from route of spread (liver or abdominal wall), GI complications (obstruction or bleeding) or response to chemotherapy (obvious decrease peritoneal thickening) from metastatic renal pelvis carcinoma patients. Pretherapy CT scan with peritoneal thickening should be alert that tumor has spread to the peritoneum.     

Diagnosis of pulmonary Kaposi's sarcoma with fiberoptic bronchoscopy and endobronchial biopsy. A report of five cases

Fiberoptic bronchoscopy is a major tool in the diagnostic evaluation of pulmonary disease in patients with the Acquired Immune Deficiency Syndrome. Multiple opportunistic infections and Kaposi's sarcoma affect the lung in this disorder. In contrast to opportunistic infections, Kaposi's sarcoma is rarely reported to be diagnosed by means of bronchoscopy. This report describes five of seven patients in whom endobronchial lesions consistent with submucosal involvement by the tumor were seen, and Kaposi's sarcoma was diagnosed without complication. Kaposi's sarcoma must be considered in the differential diagnosis of pulmonary disease in patients with a proven extrapulmonary tumor focus, and fiberoptic bronchoscopy is the initial diagnostic procedure of choice. Endobronchial Kaposi's sarcoma may be a marker for parenchymal involvement by the tumor. Diagnosis of endobronchial Kaposi's sarcoma can be an important factor in decisions regarding therapy.     

A case of endobronchial squamous cell lung cancer successfully treated with weekly chemotherapy of carboplatin and paclitaxel

A 69-year-old man had undergone low anterior resection and a right lobe resection of the liver for rectum cancer and metastatic liver tumor at the age of 66 years. He presented at our hospital because of an abnormal shadow on a CT chest scan, which indicated a tumor shadow 2.5 cm in size in the lingular lobe and enlarged hilar and mediastinal lymph nodes. A bronchoscopic tumor biopsy revealed pulmonary metastasis from the rectum cancer. Bronchoscopic examination also identified an endobronchial squamous cell lung cancer, which almost completely obstructed the orifice of B1 and B2. We concluded that the patient had squamous cell lung cancer with metastases in the mediastinal lymph nodes. He was initially treated with weekly chemotherapy with carboplatin (AUC 1.25) and paclitaxel (70 mg/m2). The endobronchial tumor was markedly reduced in size after 2 weeks of the chemotherapy. Furthermore, after 6 weeks of the chemotherapy, the tumor had disappeared completely, and 11 days later, lower division segmentectomy and hilar and mediastinal lymph node dissection were performed. Pathological examination revealed no metastases in the lymph nodes. The patient has continued to receive chemotherapy as an outpatient and has been well without recurrence of any metastases for over 16 months.     

Intraluminal low-dose rate brachytherapy for malignant endobronchial obstruction.

From October 1985 through October 1989, 87 patients underwent 105 intraluminal brachytherapy treatments for endobronchial or endotracheal malignant tumors. Low-dose rate iridium-192 seeds were used. Of the 60 patients treated for primary lung carcinoma, 52 patients (87%) had previously received full-course external beam radiotherapy to the tumor sites. Ten patients were treated for symptomatic metastatic disease, and one patient had extension of tumor into the trachea from carcinoma of the cervical esophagus. Clinical or bronchoscopic improvement was noted in 42 patients (59%). No significant difference in the response rate was observed between various types of tumor. Patients who were treated with a radiation dose larger than 2500 cGy at a 2 cm radius had a significantly greater response rate (77%) than patients treated with a dose less than 2500 cGy (38%) (p = 0.001). A trend toward better results was apparent in patients who had undergone Nd:YAG laser bronchoscopy in the 2 weeks before brachytherapy. The treatments were well tolerated, and the incidence of serious complications was low and acceptable.     

Endoscopic treatment of lung cancer]

There are many kinds of endoscopic treatment for lung cancer. In this paper the authors describe these methods and present representative cases. The first is laser treatment. There are three methods of endoscopic laser treatment. One is vaporization using high-power lasers, for example, the Nd-YAG laser. Indications for high-power laser treatment include obstructive lesions of the trachea or large bronchi with no recognizable peripheral focus. The second is photodynamic therapy (PDT) using tumor-specific photosensitizers, and low-power lasers. PDT has potential for the treatment of early stage lung cancer. The third is "laser chemotherapy," which is a new method developed by the authors using low-power lasers, e.g., He-Ne lasers, combined with chemotherapy. It is possible that antitumor drugs could be administered in doses lower than used at present. The second method is bronchofiberscopic ethanol injection therapy for stenosis or obstruction of central airways in order to obtain airway dilatation or hemostasis. The third method is brachytherapy or endobronchial radiation for central type lung cancer. We use a bronchofiberscope to place the applicator into the target bronchial lumen. Radiation therapy is performed with 60Co high dose-rate endobronchial radiation by a remote after-loading system. The value of laser treatment has been amply demonstrated and the other methods are also yielding encouraging results in the treatment of lung cancer.     

The role of combined bronchoscopic examination in the diagnosis of central peribronchial lung cancer

A complex bronchoscopic study was conducted in 315 cases of central (predominantly peribronchial) cancer of the lung. Bronchial stenosis was diagnosed in all patients. Basic bronchoscopic signs of cancer-involved stenosis were described and the following three patterns--typical, relatively typical and atypical--were identified. The report discusses a rational combination of broncho-bioptic methods of examination as well as the sequence of their application depending on degree of stenosis, tumor site and orientation of affected bronchial branches. The following procedures are instrumental in reliable cytomorphological confirmation of bronchial cancer: fibrobronchoscopy or combined application of rigid and elastic endoscopes in T1 tumor; combined or rigid bronchoscopy in T2 and rigid bronchoscopy only in T3 tumor.     

Photodynamic therapy of endobronchial malignancies

Forty-nine tumor sites in 31 consecutive patients with tracheobronchial malignant neoplasms were treated with photodynamic therapy (PDT). After sensitization with the intravenous hematoporphyrin derivative (HpD) or its more purified form of dihematoporphyrin ether (DHE), 630 nm of light from a tunable sensitizer argon light system was delivered to the tumor site through the biopsy channel of a flexible bronchoscope. All patients had received, refused, or were ineligible for conventional surgery, ionizing radiation therapy, or chemotherapy. Before or at 1 month after each treatment, tumor response was evaluated according to the following categories: (1) complete response (CR) (no visible abnormality, and negative biopsy specimen and cytology); (2) partial response (PR) (degree of obstruction or size of tumor reduced more than 50%); (3) some response (SR) (degree of obstruction or size of tumor reduced 20% to 50%); and (4) progression (PROG) (degree of obstruction or size of tumor reduced by less than 20%). Results were as follows: (1) 37% of the tumors treated achieved CR; (2) 55% achieved PR; (3) 4% achieved SR; and (4) 4% were categorized as PROG. Complete follow-up was achieved in all patients. Clinical effect was evaluated 1 month after treatment by comparing the Karnofsky performance status (KPS), dyspnea level, oxygen requirement, and presence of symptoms. Sixty-eight percent had clinical improvement in at least one variable and 48% in two or more variables. The results of this study suggest that PDT can play a useful role in the treatment of endobronchial malignancies.     

Interventionelle Therapie

Patients with lung cancer often have bulky endobronchial disease, endobronchial extension, or airway compression. Many endobronchial treatment modalities are available to supplement traditional therapies for advanced lung cancer. Since the early 1980s, technical advances in interventional techniques have enhanced symptom-free survival and quality of life for patients with lung cancer. Although interventional procedures are not definitive therapies, they often relieve the strangling sensation produced by airway occlusion. For patients with respiratory symptoms associated with their disease, these interventions provide symptom palliation and improved quality of life. The authors review the use of several endobronchial treatment modalities including rigid and flexible bronchoscopy, laser therapy, endobronchial prosthesis, and photodynamic therapy.     

Life-threatening airway obstruction at the presentation of Hodgkin's disease

Mediastinal involvement from Hodgkin's disease is common. Significant symptoms resulting from disease at this site are less common and only rarely does severe airway obstruction occur. The authors report six cases of Hodgkin's disease in which life-threatening airway obstruction was a major feature of the clinical presentation and early clinical course. The literature describing this complication is reviewed. General anesthesia with endobronchial intubation should be avoided if at all possible in patients with airway obstruction and alternative methods of diagnosis and management are discussed.