Occult Lung Cancer Research Articles

High prevalence of occult endobronchial malignancy in high risk patients with moderate sputum atypia

Early stage radiographically occult lung cancer has a high cure rate, but comprises a small fraction of all lung cancer. Abnormal sputum cytology is one indication for bronchoscopy in patients with chest imaging that is not suspicious for lung cancer. While there is good evidence that sputum cytologic findings of carcinoma, carcinoma in situ or severe atypia predict high rates of diagnosis of lung cancer, less is known of the frequency in which lung cancer is diagnosed in bronchoscopies carried out for the indication of moderate sputum atypia. One small series, published in abstract form only, reported an 8% rate of diagnosis of lung cancer in subjects bronchoscoped for moderate atypia. We tested the hypothesis that moderate sputum atypia is an indicator of occult central airway cancer in a retrospective analysis of a group of high risk subjects, defined as current or former smokers with >30 pack-years tobacco smoking and airflow obstruction with moderate atypia sputum cytology. Seventy-nine such subjects with no evidence of malignancy on chest radiograph at the time bronchoscopy was scheduled underwent white light and autofluorescence bronchoscopy. Lung cancer was found in five subjects; three had invasive squamous cell carcinomas and two had carcinoma in situ. Seven additional subjects had severe dysplasia found on endobronchial biopsy. Moderate sputum atypia may be an important marker of risk for occult endobronchial malignancy in high risk subjects.

Synchronous lesions detected by autofluorescence bronchoscopy in patients with high-grade preinvasive lesions and occult invasive squamous cell carcinoma of the proximal airways

The cancerisation field concept implies that lung cancer multicentricity may be a frequent event and primary studies using white-light bronchoscopy (WLB) have reported a high prevalence of multicentricity in patients with roentgenographically occult lung cancer. We have used autofluorescence bronchoscopy (AFB) to reassess the prevalence of synchronous lesions in patients referred for the staging and/or treatment of occult lesions initially detected during WLB. All the patients referred with high-grade preinvasive lesions (severe dysplasia, DYS S and carcinoma in situ, CIS) and occult invasive squamous cell carcinoma (CIV) of the bronchus initially detected during WLB at other centers, underwent AFB. Data were prospectively collected and retrospectively analyzed to assess the prevalence of synchronous occult lesions. From January 1996 to December 2001, 28 patients (26 males, 2 females; mean age: 65 ± 11) were assessed. After re-evaluation, in two cases, the referred lesions corresponded only to metaplasia and were discarded from analysis. The 26 other patients were referred for 28 lesions (3 DYS S, 19 CIS and 6 CIV; 2 patients were referred with two synchronous lesions). AFB revealed, in these 26 patients, six additional lesions (1 DYS S, 4 CIS and 1 CIV). Multicentricity in this group, initially estimated to amount to 7% with WLB alone, raised to 23% by using AFB. The high prevalence of synchronous lesions in this series of patients with occult DYS S, CIS and occult CIV suggests that AFB may be a useful adjunct in the pretreatment evaluation.

P-266 Evaluation of first line photodynamic therapy (PDT) in roentgenographycally occult central lung cancers (ROC)

P-266 Evaluation of first line photodynamic therapy (PDT) in roentgenographycally occult central lung cancers (ROC)

Sputum cytology for the detection of early lung cancer.

Sputum cytology is an important step in the early diagnosis of roentgenographically occult lung cancer. It identifies primarily intraepithelial lesions, which are the most common squamous carcinomas not detected by helical CT. Patients at highest risk for lung cancer (eg, heavy smokers with airflow obstruction) should undergo sputum cytology. Patients with premalignant lesions (eg, moderate or severe dysplasia) and of course patients with carcinoma in situ or invasive carcinoma should receive fiberoptic bronchoscopy. The diagnosis and treatment of early-stage lung cancer usually has a favorable outcome. Today we have the knowledge and technology that can change the outcome of lung cancer through early identification, particularly in high-risk patients.

Bronchoscopic treatment of patients with intraluminal microinvasive radiographically occult lung cancer not eligible for surgical resection

Comments: This publication provides long-term followup in a group of 32 patients who underwent bronchoscopic treatment (BT) for the treatment of intraluminal microinvasive radiographically occult lung cancer (ROLC). These patients were not eligible for surgical resection because of comorbidities and other reasons. These 32 patients (28 men and 4 women) met the following inclusion criteria for the study: surgically nonresectable candidates because of poor lung function or the presence of multiple primaries; a strictly ≤ 1 cm in size, intraluminal, microinvasive ROLC (carcinoma in situ excluded) with visible distal tumor margin by conventional and autofluorescence bronchoscopy; no bronchial wall invasion or extraluminal tumor growth on highresolution computed tomography. History of prior primary lung cancer was present in 13 patients, and these were surgically resected as long as 13 years before current synchronous or metachronous primaries. The TNM stages of previous resections for the non-ROLC tumors were stage IB in seven patients, stage IIB in four patients, stage IIIA in one patient, and stage IIIB in one patient. There was no sign of recurrence or metastatic disease of the previous non-ROLC cancer before BT. In six patients, multiple ROLCs were found at different sites in both lungs (four patients with two lesions and two patients with three lesions) that met all criteria for BT as described earlier. BT was administered with intent to cure cancer, and consecutive patients were treated with photodynamic therapy (n = 5), Nd:YAG laser therapy (n = 1), electrocautery (n = 24), and argon plasma coagulation (n = 2). Follow-up evaluation at 3 to 4 months interval included high-resolution computed tomographic scans, both conventional and autofluorescence bronchoscopy, including biopsy specimens and brush cytology for histologic evaluation. The average follow-up period was 5 years (range, 2–10 years). In three patients local recurrence was again successfully treated with electrocautery. Sixteen patients (50%) died during follow-up. Eight of the nine patients who died as a result of lung cancer had a previous resection of a more advanced stage lung cancer as long as 5 years before BT of the ROLC. In the remaining seven patients, the cause of death was not related to lung cancer. Sixteen patients are still alive without any tumor recurrence. Based on these observations, the authors conclude that BT is an effective treatment modality for high-risk patients with ROLC who are not eligible for surgical resection. Early detection of lung cancer by currently available methods such as low-dose spiral computed tomography, screening sputum cytology, autofluorescence bronchoscopy, and other techniques may enable surgical cure in a number of patients. However, not all patients are surgical candidates because of various reasons. One of the main reasons is the presence of cancer in the major airways (trachea and within 2.0 cm of the main carina), which upgrades the cancer stage. More commonly, surgery and anesthesia are contraindicated because of underlying medical conditions such as severe chronic obstructive pulmonary disease, severe malnutrition, and other conditions. When such patients develop intraluminal microinvasive ROLC in the central part of the tracheabronchial tree, various types of BT described in this publication may benefit them. Nonetheless, as noted by the authors of this study, early detection of lung cancer and BT in such patients is questionable because this expensive and time-consuming exercise may have little or no impact on mortality. Death from lung cancer occurred in 9 patients (28%), and death from other causes was noted in 7 patients (22%). The positive outcome of this study is that 50% of patients were still alive after BT, with an average follow-up of 5 years (range, 2–10 years).

Is Autofluorescence Bronchoscopy Needed to Diagnose Early Bronchogenic Carcinoma?

Is Autofluorescence Bronchoscopy Needed to Diagnose Early Bronchogenic Carcinoma?

Bronchoscopic treatment of patients with intraluminal microinvasive radiographically occult lung cancer not eligible for surgical resection: a follow-up study

Bronchoscopic treatment (BT) has a curative potential for patients with intraluminal microinvasive radiographically occult lung cancer (ROLC). We report the long-term follow-up in a group of 32 patients, ineligible for surgery, in whom ROLC was diagnosed and treated with BT. Tumors were strictly ⩽1 cm in size, intraluminally located in the central airways, with no bronchial wall invasion or extraluminal tumor growth on high resolution CT (HRCT), with visible distal margin under conventional and autofluorescence bronchoscopy (AFB). BT was given with curative intent and consecutive patients were treated with photodynamic therapy (five patients), Nd-YAG laser therapy (one patient), electrocautery (24 patients) and argon plasma coagulation (two patients). Follow-up evaluation at 3–4 months interval included HRCT scans, both conventional and AFB, including biopsies and brush cytology for histological evaluation. The average follow-up period was 5 years (range: 2–10 years). In three patients local recurrence was again successfully treated with electrocautery. Sixteen patients died during follow-up. Eight of the nine patients who died due to lung cancer had a previous resection of a more advanced stage lung cancer up to 5 years before BT of the ROLC. The remaining seven patients cause of death was not related to lung cancer. Sixteen patients are still alive without any tumor recurrence. These data showed that BT is an effective treatment modality for high-risk patients with ROLC, who are not eligible for surgical resection.

New concepts in lung cancer screening.

Although spiral CT has an undeniably impressive ability to detect occult lung cancers in asymptomatic smokers, it is not clear whether screening this patient group will lead to a reduction in disease-specific mortality. The specter of overdiagnosis in lung cancer screening, which manifested during the chest radiograph trials of the 1970s and 1980s, still hangs over screening regimes today. The detection of premalignant lesions by molecular medicine techniques and fluorescence bronchoscopy may allow the development of novel treatments for preinvasive disease, but it is likely that radiologic means of detection will form the front line of any near future screening program. The proposed screening techniques may be new, but their use must be tested against tried and trusted standards of medical practice.

88 poster CT-assisted endobronchial brachytherapy for roentgenographycally occult lung cancer

88 poster CT-assisted endobronchial brachytherapy for roentgenographycally occult lung cancer

Autofluorescence bronchoscopy improves staging of radiographically occult lung cancer and has an impact on therapeutic strategy.

Autofluorescence bronchoscopy improves staging of radiographically occult lung cancer and has an impact on therapeutic strategy.

Autofluorescence Bronchoscopy Improves Staging of Radiographically Occult Lung Cancer and Has an Impact on Therapeutic Strategy

The ability of conventional CT scans and fiberoptic bronchoscopy to localize and properly stage radiographically occult lung cancer (ROLC) in the major airways is limited. High-resolution CT (HRCT) scanning and autofluorescence bronchoscopy (AFB) may improve the assessment of ROLC before the most appropriate therapy can be considered. We prospectively studied 23 patients with ROLC, who were referred for intraluminal bronchoscopic treatment (IBT) with curative intent. Additional staging with HRCT and AFB was performed prior to treatment. Twenty patients were men, 9 patients had first primary cancers, and 14 patients had second primary cancers or synchronous cancers. HRCT scanning showed that 19 patients (83%) had no visible tumor or enlarged lymph nodes. With AFB, only 6 of the 19 patients (32%) proved to have tumors < or = 1 cm(2) with visible distal margins. They were treated with IBT. In the remaining 13 patients, abnormal fluorescence indicated more extensive tumor infiltration than could be seen with conventional bronchoscopy alone. Six patients underwent radical surgery for stage T1-2N0 (n = 5) and stage T2N1 (n = 1) tumors. Specimens showed that tumors were indeed more invasive than initially expected. The remaining seven patients technically did not have operable conditions, so they were treated with external irradiation (n = 4) and IBT (n = 3). The range for the time of follow-up for all patients has been 4 to 58 months (median, 40 months). The follow-up data underscore the correlation between accurate tumor staging and survival. Our data showed that 70% of patients presenting with ROLC had a more advanced cancer than that initially diagnosed, which precludes IBT with curative intent. Additional staging with HRCT and AFB enabled better classification of true occult cancers. Our approach enabled the choice of the most appropriate therapy for each individual patient with ROLC.

Paraparesia secundaria a metástasis intramedular como manifestación inicial de un carcinoma microcítico de pulmón

Intramedullary metastases (IM) are uncommon and rarely considered the initial presentation of malignancy. Lung and breast cancer account for most of the primary tumors. Magnetic resonance imaging may facilitate recognition of IM in patients with clinical features of myelopathy. A case of a unique intramedullary metastases as the presenting feature of an occult lung cancer is described.

External irradiation and intraluminal irradiation using middle-dose-rate iridium in patients with roentgenographically occult lung cancer

Purpose: Therapeutic results were analyzed in 39 patients with roentgenographically occult lung cancer (ROLC), and the significance and optimal dose of this therapy were evaluated. Methods and Materials: The subjects were 39 patients who underwent intraluminal irradiation between May 1987 and August 1999. Radiotherapy was performed by combining external irradiation with intraluminal irradiation using middle-dose-rate iridium (four 370-MBq wires) through a catheter with a spacer, which held the source in the center of the bronchus. The doses of radiation were 22–66 Gy (median value 45 Gy) by external irradiation and 10–46 Gy (median value 28 Gy) by intraluminal irradiation. Results: The therapeutic effect was CR in 38 patients and PR in 1, and local recurrence was observed in a PR case and 3 of the 38 patients who showed CR. The 3-year and 5-year relapse-free survival rates were both 87%. No severe radiation injury was observed. Conclusions: Considering that ROLC often occurs as multiple cancers and that many patients with ROLC have reduced lung function, radiation therapy by a combination of intraluminal irradiation and external irradiation is expected to replace surgery as the first choice for the treatment of this disease in the twenty-first century.

Five year survival and later outcome of patients with X-ray occult lung cancer detected by sputum cytology

Background: A cohort of 51 consecutive patients with roentgenographically occult lung cancer, identified by sputum cytology and confirmed by bronchoscopy was reported previously. Methods: All patients have now been followed beyond 5 years and the causes of death ascertained. Results: The actual 5-year survival of 27 patients who were resected for cure was 74% including death for all causes. The 5-year survival of all patients who received either surgery or radiation in an attempt to cure was 54.3%. Twelve secondary cancers were found by sputum cytology; eight of these patients have died. Conclusions: Sputum cytology can be useful in the identification of early stage lung cancer in patients at high-risk where the chances of cure are favorable.

Surgical results for centrally-located early stage lung cancer

Background. With the increasing use of mass screening programs for lung cancer, and especially the use of sputum cytology, the incidence of roentgenographically occult lung cancer has been increasing. These occult cancers comprise mainly histologically centrally-located early stage lung cancers. This study examined the clinicopathologic characteristics and surgical results of centrally-located early stage lung cancer. Results. From 1980 to 1998, there were 98 patients and 99 lesions of centrally-located early stage lung cancer resected. A total of 64 patients were detected by mass screening. Histologic examination revealed that 96 lesions were squamous cell carcinoma, and in these patients, there were 10 lesions of carcinoma in situ. The 5-year survival rate was 81.4% in all patients, and 88.9% in carcinoma in situ patients. In the postoperative follow-up period, a second lung cancer occurred in 13 patients. Conclusions. The surgical results for centrally-located early lung cancer were good. However, sometimes these cancers are accompanied by a second centrally-located primary lung cancer, so it is necessary to follow-up with sputum cytology to allow early detection of additional centrally-located lung cancer.

The treatment results of 40 patients with localized endobronchial cancer with external beam irradiation and intraluminal irradiation using low dose rate 192Ir thin wires with a new catheter

Background and purpose: While bronchial intraluminal irradiation is valued highly as a useful palliative treatment for lung cancer, its role as a curative treatment is unclear. The treatment results of 40 localized enbobronchial tumors (including tracheal cancer) who underwent external beam irradiation (EBR) and intraluminal irradiation (IR) as a curative treatment is reported, and the role of combined EBR and IR as a curative potential treatment is examined. Materials and methods: Forty patients, including 22 with roentgenographically occult lung cancer (ROLC), 14 (18 lesions) with postoperative recurrent lung cancer (PORLC) and four with tracheal cancer, who underwent EBR and IR from February 1987 to August 1996, were studied. IR was conducted using low dose rate (1.48 GBq) 192Ir thin wires at a bronchial mucosal dose of 4–6 Gy per fraction, with a total dose of 10–57 Gy (median 28 Gy). All patients were also given combined external Linac X-ray irradiation for a total dose of 30–77 Gy (median 52 Gy). Results: As for the primary effect, complete response (CR) was obtained in all 22 ROLC cases; CR was obtained in 12 (16 lesions), partial response (PR) in one and minor response (MR) in one of the PORLC cases; and CR was obtained in three and PR in one of the tracheal cancer cases. The 3-year and 5-year local control rate by Kaplan–Meier method was 75 and 65%, respectively. Twenty-two patients survived for 3 years or longer. Complications included one case each of fatal tracheal hemorrhage, bronchial mucosal ulcer and bronchial stenosis. Conclusions: Combined EBR and IR is useful as a curative potential treatment, and long-term survival can be expected in ROLC, tracheal cancer and a portion of PORLC cases.

Radiation therapy for roentogenographically occult lung cancer by external beam irradiation and endobronchial high dose rate brachytherapy

Purpose: We investigated the clinical usefulness of radiation therapy by external beam irradiation and endobronchial brachytherapy for the treatment of roentogenographically occult lung cancer. Patients and methods: From 1995 to 1996, five patients were treated with radiation therapy. We analyzed their treatment outcomes. The follow-up period varied from 3.0 to 3.8 years or until death. External beam radiation (40 Gy/20 fractions/4 weeks) was delivered to the tumor site alone, and not prophylactically given to the mediastinum. Endobronchial brachytherapy using high dose rate iridium (Ir)-192 was concurrently administered principally to a total dose of 18 Gy on the bronchial mucosa in three weekly fractions of 6 Gy each. Results: Complete remission was obtained in all patients. Two patients died of intercurrent diseases at 12 and 21 months without any evidence of recurrence. The disease has been also controlled in the other three cases. With the above doses, three small tumors <1 cm were controlled without adverse effect. In two tumors, the dose reference points were set 2–7 mm beneath the mucosa, and larger doses were administered by brachytherapy. An applicator acting as a spacer was not used in these cases. The tumors were controlled, although the irradiated bronchi showed severe stenosis in 6 months following the treatment. However, the patients were asymptomatic and did not need further intervention. Conclusion: External beam irradiation combined with endobronchial brachytherapy was useful for the treatment of roentogenographically occult lung cancer as an alternative to surgery. Further investigation is needed to determine the optimal doses of radiation therapy.

The influence of lung cancer mass screening on surgical results

Background: After the introduction of the mass screening program for lung cancer, the number of patients detected by mass screening increased as well as the number of early staged patients. Therefore, we examined the influence of lung cancer mass screening on surgical results. Methods: A total of 1177 primary lung cancer cases, who underwent surgery from 1963 to 1992, were retrospectively reviewed. They were grouped according to the changes in the mass screening system: the first period (1963–1977) before lung cancer screening started, the second period (1978–1986) when mass screening was conducted by the local government, and the third period (1987–1992) after the launching of the national screening program. Results: The rate of cases detected by mass screening increased over time and the 5-year survival rate improved significantly, from 33.7% in the first period, to 51.8% in the second period and finally, to 58.4% in the third period. The improvement is attributable to a relative increase of rate of stage I cases and better stage I survival rate. Specifically, in stage I cases, improvement resulted from a relative increase of stage IA in peripheral type and roentgenographically occult lung cancer cases and from better survival rate of these two groups. Conclusion: As lung cancer screening has come into widespread use, detection of peripheral small-sized lung cancer and roentgenographically occult lung cancer have increased and consequently, surgical results have improved.

721 Second primary tumor (SPT) of patients (PTS) with roentgenologically occult lung cancer (ROLC) treated with photodynamic therapy (PDT)

721 Second primary tumor (SPT) of patients (PTS) with roentgenologically occult lung cancer (ROLC) treated with photodynamic therapy (PDT)

479 A phase II study of combined endobronchial low-dose rate brachytherapy (EBT) and external beam radiotherapy (ER) for roentgenographically occult lung cancer

479 A phase II study of combined endobronchial low-dose rate brachytherapy (EBT) and external beam radiotherapy (ER) for roentgenographically occult lung cancer