Relationship Between Corticosteroid Administration and Survival Period in Terminal Cancer Patients.

Objective: Corticosteroids are commonly used for symptom relief in patients with terminal cancer, but their use may have an impact on patient survival. We compared the survival of patients with terminal cancer who did and did not receive corticosteroid treatment for symptom relief, stratified by their predicted prognosis. Methods: We retrospectively reviewed consecutive patients with cancer who received corticosteroid treatment for symptom relief in a single palliative care unit. We stratified the patients according to their predicted prognosis using the palliative prognostic (PaP) score either before starting the corticosteroid treatment or at admission for control patients who did not receive a corticosteroid treatment. The 2 groups were compared for survival based on the PaP Scores. Results: We analyzed 204 patients treated with a corticosteroid during the study period and 139 control patients who did not receive corticosteroids during their treatment. No difference was observed in the survival between the treatment and control groups. Conclusion: Corticosteroid treatment for symptom relief in patients with terminal cancer did not affect survival time.

A quantitative analysis of long-term follow-up computed tomography of idiopathic pulmonary fibrosis: the correlation with the progression and prognosis.

BACKGROUND: Quantitative analyses of computed tomography (CT) images using computer-aided detection (CAD) are correlated with visual assessments and pulmonary function test findings and might be useful for predicting the prognosis of patients with idiopathic pulmonary fibrosis (IPF). PURPOSE: To evaluate the association between the quantitative analysis of long-term follow-up CT of IPF and the progression and prognosis. MATERIAL AND METHODS: A total of 48 patients with IPF who received over one year of follow-up CT were included in this study. The results of quantitative analyses (emphysema, ground-glass attenuation [GGA], consolidation, reticulation, and honeycombing) using a CAD software program of initial and follow-up CT findings were evaluated, and the association with the progression of the total lesion of IPF and prognosis using Spearman's rank correlation and Cox regression analyses was considered. RESULTS: Results of quantitative analyses of consolidation, reticulation, honeycombing, and the total lesion on initial CT were correlated with progressive changes in the total lesion of IPF per year (r = 0.4375, 0.4128, 0.4649, and 0.4095, respectively). The results of quantitative analyses of honeycombing (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.03-1.89, P = 0.0314) and GGA (HR = 0.85, 95% CI = 0.72-0.99, P = 0.0384) at initial CT were prognostic factors according to a multivariate Cox regression analysis. CONCLUSION: The quantitative analysis of honeycombing using a CAD software program of CT findings may be useful for predicting the progression and prognosis of patients with IPF.

Cytokine Adsorption to Polymyxin B-Immobilized Fiber: An in vitro Study.

BACKGROUND: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are episodes of acute respiratory worsening characterized by diffuse alveolar damage superimposed on usual interstitial pneumonia. Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) is reported to have beneficial effects on the respiratory status and outcome in patients with AE-IPF although its mechanism of action is not fully elucidated. OBJECTIVE: To investigate whether and how the PMX-immobilized fiber (PMX-F) adsorbs cytokines because reduction of the serum levels of various cytokines has been noted in AE-IPF patients receiving PMX-DHP. METHODS: The propensity of recombinant cytokines for adsorption onto PMX-F was examined by incubating cytokines with heparin-coated or uncoated PMX-F for 2 h at 37°C. Cytokines were quantitated by multiplex bead array assay or ELISA. RESULTS: Interleukin (IL)-8, RANTES, platelet-derived growth factor-bb, and transforming growth factor-ß were substantially adsorbed onto PMX-F without heparin coating. The adsorbed cytokines could be eluted with PMX sulfate, indicating that the PMX moiety is involved in cytokine adsorption. Importantly, although IL-1ß, monocyte chemoattractant protein-1, fibroblast growth factor 2, and vascular endothelial growth factor-A were adsorbed onto PMX-F to lesser extents, the adsorption was enhanced by heparin coating of PMX-F. Furthermore, heparin-coated PMX-F acquired the capability to adsorb IL-6, IL-12, and tumor necrosis factor α. An affinity of heparin to PMX was determined (Kd = 0.061 ± 0.032 mg/mL), which accounts for the enhanced cytokine adsorption onto PMX-F upon heparin coating. CONCLUSIONS: Various cytokines involved in inflammation, fibrosis, and vascular permeability were shown to be adsorbed onto PMX-F. Removal of multiple cytokines may be associated with positive impacts of PMX-DHP in patients with AE-IPF.

Variations in the Efficiency of Albuterol Delivery and Intrapulmonary Effects With Differential Parameter Settings on Intrapulmonary Percussive Ventilation.

BACKGROUND: Intrapulmonary percussive ventilation (IPV) is used for airway clearance and delivery of aerosol medications, including bronchodilators. Despite the common use of IPV for drug delivery, few data are available regarding optimization of inhalation therapy with IPV. In this study, we investigated the influence of IPV setting parameters and lung mechanics on drug delivery via IPV alone. METHODS: An IPV device was connected to a lung model via a trachea model and a flow analyzer. Albuterol nebulized from the IPV device was collected onto a filter attached between the trachea and lung models, and was quantitated by spectrophotometry (230 nm). RESULTS: Albuterol delivery to the lung model was increased up to 2.1-fold, with decreasing percussion frequency. Decreasing percussion frequency concomitantly increased the tidal volume, and albuterol delivery was correlated with tidal volume (r = 0.91, P < .001). Airway resistance had a negative impact on albuterol delivery, whereas lung compliance had no significant effect. Increasing operational pressure increased albuterol delivery while increasing peak inspiratory pressure. CONCLUSIONS: Albuterol delivery and tidal volume with IPV can be improved by maintaining low levels of percussion frequency and increasing operational pressure. When increasing operational pressure, the peak inspiratory pressure and airway resistance levels need to be carefully monitored for safe inhalation therapy with IPV.

A phase II study of topotecan and cisplatin with sequential thoracic radiotherapy in elderly patients with small-cell lung cancer: Okayama Lung Cancer Study Group 0102.

PURPOSE: The treatment outcome in elderly patients with limited-disease small-cell lung cancer (LD-SCLC) remains poor. We carried out a phase II trial of split topotecan and cisplatin (TP) therapy and sequential thoracic radiotherapy for elderly LD-SCLC patients as a follow-up to our previous phase I trial. METHODS: In total, 30 patients aged 76 years or older, with untreated LD-SCLC were enrolled. Four courses of topotecan (1.0 mg/m(2), days 1-3) and cisplatin (20 mg/m(2), days 1-3) were administered, followed by thoracic radiotherapy (1.8 Gy/day, total of 45 Gy). The primary end point was the overall response rate (ORR). RESULTS: The trial was terminated early with 22 patients because of slow accrual. Their median age was 79 years. The median number of courses of chemotherapy administered was three, and the actual completion rate of the entire treatment course was 41 %. The ORR was 68 % with a 95 % confidence interval of 47-89 % (15/22 cases). The median progression-free survival and overall survival were 9.1 and 22.2 months, respectively. The main toxicity was myelosuppression, with grades 3-4 neutropenia (96 %), thrombocytopenia (50 %), and febrile neutropenia (32 %). CONCLUSIONS: This regimen produced a favorable survival outcome, despite moderate-to-severe toxicity profiles. Further efforts are necessary to define an optimal regimen for elderly patients with limited SCLC.

[Awareness about medical expenses and certifications of eligibility for limited health insurance payments for chemotherapy among clinicians at the Ehime Cancer Care Network Priority Hospitals (Ehime Cancer Kyoten Hospitals)].

The "Cancer Chemotherapy and its Management" subcommittee at the Ehime Cancer Care Network Priority Hospitals (Ehime Cancer Kyoten Hospitals)with a focus on medical expenses associated with chemotherapy, surveyed awareness among 98 clinicians regarding certifications of eligibility for Limited Health Insurance Payments during cancer treatment. This committee also lists social and clinical problems encountered at the Ehime Cancer Care Network Priority Hospitals. In our survey, 78% of clinicians were consulted about medical expenses associated with chemotherapy and were actively involved in resolving medical expense problems and resulting correspondences. However, only 38% of clinicians could explain the details of the Japanese guideline on the catastrophic cap and the certifications of eligibility for Limited Health Insurance Payments. This knowledge deficit was more pronounced in younger residents. From our analyses of the awareness about medical expenses among clinicians, we recommend the establishment of the following systems for the management of cancer patients. First, establish a reporting system and early consultation on the catastrophic cap and the certifications of eligibility before initiating cancer treatment. Second, education regarding medical expenses should be mandatory for clinicians, especially for young residents. Third, patients with cancer suffering in the interval of the medical expense and the social system should be relieved with new systems.

Clinical outcome in patients with leptomeningeal metastasis from non-small cell lung cancer: Okayama Lung Cancer Study Group.

OBJECTIVE: We examined the prognosis of patients with leptomeningeal metastasis (LM) from non-small cell lung cancer (NSCLC) and that stratified by epidermal growth factor receptor (EGFR) mutation status in LM patients receiving EGFR-tyrosine kinase inhibitors (TKIs). METHODS: We retrospectively analyzed a series of 91 consecutive NSCLC patients with LM between 2001 and 2010. RESULTS: Most of the LM patients had adenocarcinoma histology and a poor performance status (PS). The median survival time (MST) for all patients was 3.6 months. Adenocarcinoma and TKI treatment were associated with a better prognosis. Among the patients, 51 received EGFR-TKIs. Of these, the EGFR mutation status was assessed in 30 patients; 7 (23%) showed no mutation (group 1), 10 (33%) had a mutation in exon 21 (group 2), and 13 (43%) had deletions in exon 19 (group 3). Interestingly, PS was significantly improved in groups 2 and 3 but not in group 1. The MST in these subgroups was 1.4, 7.1, and 11.0 months in groups 1, 2, and 3, respectively (p<0.001). The median time to progression or symptom deterioration was 0.9, 2.0, and 7.8 months for groups 1, 2, and 3, respectively (p<0.001). A multivariate analysis showed that EGFR-mutant tumors were associated with a better prognosis in patients receiving EGFR-TKIs. CONCLUSIONS: The prognosis for patients with LM from NSCLC was still poor. Survival after the initiation of EGFR-TKI treatment differed according to the type of EGFR mutation, suggesting the potential benefit of TKIs for patients with EGFR mutations, even though they suffered from LM.

Long-term follow-up of phase II trial of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small cell lung cancer.

BACKGROUND: Chemoradiation improves survival for patients with locally advanced non-small cell lung cancer (NSCLC), but clinical outcomes beyond five years are rarely reported. The aim of the present study was to identify the long-term results of a phase II study of docetaxel and cisplatin with concurrent thoracic radiation. METHODS: We previously reported short-term outcomes from the phase II study, which enrolled 42 patients (aged ≤ 75 years) with unresectable stage III NSCLC. We continued to follow these patients for long-term clinical outcomes. RESULTS: At a median follow-up for all patients of 6.3 years (range: 5.2-7.1 years), the median survival time was 2.1 years and the actual five-year survival rate was 31%. Among 14 patients who were progression-free longer than two years, three patients died due to bacterial or fungal pneumonia and one died due to gall bladder cancer. CONCLUSIONS: Thirty-one percent of locally advanced patients having NSCLC treated with docetaxel and cisplatin and concurrent thoracic radiation survived beyond five years. Progression-free patients might be cautiously followed up taking precautions against emerging pneumonia.

Variant angina pectoris associated with FOLFOX4 therapy.

The patient was a 71-year-old man who underwent a right hemicolectomy for ascending colon cancer (pT3, pN1, pM0) and who opted not to receive adjuvant chemotherapy. Eight months later, multiple liver metastases occurred. He therefore received FOLFOX4 (5-fluorouracil/leucovorin and 85 mg/m(2) oxaliplatin) therapy, up to a total of 5 courses, and showed a partial response. While receiving the sixth course of FOLFOX4, he complained of chest pain and systemic itching approximately 15 min after the start of chemotherapy. An electrocardiogram revealed typical signs of ischemia. Coronary arteriography showed that the coronary arteries were intact. Believing the chest pain to be merely coincidental, we continued with the same therapy. However, he again developed the same chest pain during the seventh cycle of FOLFOX4 and treatment was stopped. We concluded that the patient's symptoms were due to acute coronary syndrome (ACS) associated with the FOLFOX4 regimen. Variant angina as a type of ACS is a rare adverse effect of FOLFOX4. Clinicians should be aware of this potential adverse effect when monitoring patients receiving FOLFOX4.

Interstitial lung disease associated with gemcitabine treatment in patients with non-small-cell lung cancer and pancreatic cancer.

PURPOSE: Although there are several reports concerning gemcitabine-induced interstitial lung disease (ILD), the risk factors for ILD are not well known. In addition, data comparing the incidence and pattern of ILD associated with gemcitabine treatment in patients with non-small-cell lung cancer (NSCLC) versus those with pancreatic cancer are scarce. METHODS: We reviewed clinical records of 118 patients treated with gemcitabine between November 2004 and November 2010. The radiographic findings and other relevant clinical data were reviewed to identify patients who had developed ILD associated with gemcitabine treatment. RESULTS: Out of these 118 patients, we identified 62 patients with NSCLC (group A) and 56 patients with pancreatic cancer (group B), which were then analysed. After gemcitabine administration, ILD was detected in 9 out of the total 118 patients (7.6%). Three patients had grade 2 ILD and 6 patients had grade 3 ILD. Multivariate analysis revealed that prior thoracic radiotherapy (odds ratio: 26.3) and pre-existing pulmonary fibrosis (PF) (odds ratio: 6.5) were correlated with ILD occurrence, but the incidence of ILD was not different between groups A and B. The median dose of gemcitabine administered till the manifestation of ILD tended to be lower in group A than in group B. CONCLUSIONS: Prior thoracic radiotherapy and pre-existing PF were correlated with higher ILD rate in gemcitabine-treated patients. ILD incidence did not differ between NSCLC and pancreatic cancer patients, which may be due to the differences in treatment strategy and tumour properties.

An oral fluoropyrimidine agent S-1 induced interstitial lung disease: A case report.

A 66-year-old Japanese man with pancreatic cancer received eleven courses of gemcitabine monotherapy. The tumor responded to gemcitabine until metastatic liver tumors progressed. Subsequently, he was treated with S-1, an oral fluoropyrimidine anticancer agent, as salvage chemotherapy. Forty-two days after initiating S-1, he presented with dyspnea and fever. Chest computed tomography showed diffuse interstitial lesions with thickening of the alveolar septa and ground glass opacity. Serum KL-6 level was elevated to 1,230 U/mL and he did not use any other drugs except insulin. Thus, the development of interstitial lung disease (ILD) was considered to be due to S-1. Arterial blood oxygen pressure was 49.6 Torr in spite of oxygen administration (5 L/min). Steroid therapy improved his symptoms and the interstitial shadows on chest radiograph. Although S-1-induced ILD has mostly been reported to be mild, clinicians should be aware that S-1 has the potential to cause fatal ILD.

Synchronous double primary lung cancers with different response to pemetrexed.

We describe the case of a 74-year-old male patient with synchronous double primary lung cancers: adenocarcinoma in the right lower lobe and squamous cell carcinoma in the left upper lobe (LUL). These tumors were difficult to differentiate radiographically from a single metastatic primary cancer, but their eventual diagnoses were triggered by their responses to chemotherapy, which included pemetrexed. After two courses of chemotherapy with pemetrexed and carboplatin, the right lower lobe mass had partially resolved; however, the LUL mass had increased. When S-1 was used as fourth-line chemotherapy, the size of the LUL mass decreased. Pemetrexed is a potentially useful drug for treating nonsquamous cell carcinoma, but may not be appropriate in cases with a coexisting squamous cell carcinoma. Our experience with this interesting case leads us to propose that S-1 monotherapy may provide a treatment option in pemetrexed-refractory cases.

Cavitary pulmonary involvement of diffuse large B-cell lymphoma transformed from extra nodal marginal zone B-cell lymphoma MALT type.

We describe a case of pulmonary diffuse large B-cell lymphoma (DLBCL), which was thought to arise from extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). A 68-year-old woman presented with a 2-month history of cough and bloody sputum. The chest X-ray and computed tomography revealed a mass with cavitation in the right lower lobe. Transbronchial biopsy specimens revealed a granulomatous infiltration without malignant cells. However, diagnosis of MALT lymphoma was established from gastric biopsy specimen. Subsequently, a right lower lobectomy was performed because of hemoptysis. Examination of the resected specimen revealed a diffuse large B-cell lymphoma, which was considered to have transformed from MALT lymphoma, because both lung and stomach lesions had the chromosomal translocation t(11;18)(q21;q21) in common. In addition, there were no nodules, masses, alveolar or interstitial infiltrates in the lung fields, which are usually observed in the case of marginal zone B-cell lymphoma of bronchial mucosa-associated lymphoid tissue. These findings indicate that involvement of DLBCL have to be considered in patients with MALT lymphoma and cavitary lesion of the lung.

Phase III trial comparing docetaxel and cisplatin combination chemotherapy with mitomycin, vindesine, and cisplatin combination chemotherapy with concurrent thoracic radiotherapy in locally advanced non-small-cell lung cancer: OLCSG 0007.

PURPOSE: To demonstrate the efficacy of docetaxel and cisplatin (DP) chemotherapy with concurrent thoracic radiotherapy (TRT) for patients with locally advanced non-small-cell lung cancer (LA-NSCLC). PATIENTS AND METHODS: Patients age 75 years or younger with LA-NSCLC, stratified by performance status, stage, and institution, were randomly assigned to two arms consisting of DP (docetaxel 40 mg/m(2) and cisplatin 40 mg/m(2) on days 1, 8, 29, and 36) or mitomycin, vindesine, and cisplatin (MVP) chemotherapy with concurrent TRT. RESULTS: Between July 2000 and July 2005, 200 patients were allocated into either the DP or MVP arm. The survival time at 2 years, a primary end point, was favorable to the DP arm (P = .059 by a stratified log-rank test as a planned analysis and P = .044 by an early-period, weighted log-rank as an unplanned analysis). There was a trend toward improved response rate, 2-year survival rate, median progression-free time, and median survival in the DP arm (78.8%, 60.3%,13.4 months, and 26.8 months, respectively) compared with the MVP arm (70.3%, 48.1%, 10.5 months, and 23.7 months, respectively), which was not statistically significant (P > .05). Grade 3 febrile neutropenia occurred more often in the MVP arm than in the DP arm (39% v 22%, respectively; P = .012), and grade 3 to 4 radiation esophagitis was likely to be more common in the DP arm than in the MVP arm (14% v 6%, P = .056). CONCLUSION: DP chemotherapy combined with concurrent TRT is an alternative to MVP chemotherapy for patients with LA-NSCLC.

Comparison of the incidence and pattern of interstitial lung disease during erlotinib and gefitinib treatment in Japanese Patients with non-small cell lung cancer: the Okayama Lung Cancer Study Group experience.

BACKGROUND: Data comparing the incidence and pattern of interstitial lung disease (ILD) in non-small cell lung cancer patients receiving treatment with gefitinib versus erlotinib, both of which are epidermal growth factor receptor tyrosine kinase inhibitors, are scarce. We investigated the incidence of ILD in Japanese patients treated with gefitinib or erlotinib. METHODS: We reviewed the clinical records of 209 patients treated with erlotinib in 2008 (cohort A) and 330 treated with gefitinib between 2000 and 2003 (cohort B). Toxicity within the first month of treatment was investigated. RESULTS: The patients in cohort A had fewer known risk factors for ILD (e.g., poor performance status and prior pulmonary fibrosis). ILD was detected in two patients (1.0%) from cohort A and eight patients (2.4%) from cohort B during the first month of treatment. The events were graded as follows: one patient each in grades 1 and 2 (cohort A), and one, one, and six patients in grades 3, 4, and 5, respectively (cohort B). Multivariate analysis revealed that poor performance status and prior pulmonary fibrosis were significantly correlated with the occurrence of ILD, but the type of epidermal growth factor receptor tyrosine kinase inhibitor administered was not. CONCLUSION: There was a somewhat lower incidence of ILD with erlotinib therapy than with gefitinib therapy, despite no statistically significant difference. Patient selection based on awareness by Japanese physicians of the risk factors for ILD, rather than the type of agent, may explain the difference in ILD incidence between the two treatments.

A phase II trial of erlotinib monotherapy in pretreated patients with advanced non-small cell lung cancer who do not possess active EGFR mutations: Okayama Lung Cancer Study Group trial 0705.

BACKGROUNDS: Efficacy of gefitinib therapy strongly depends on epidermal growth factor receptor (EGFR)-mutation status in Asian patients with non-small cell lung cancer. Recently, the survival advantage of erlotinib, another tyrosine kinase inhibitor, was not affected by EGFR mutation status in a phase III trial, indicating that patients with EGFR-wild-type (EGFR-wt) tumors might also benefit from this tyrosine kinase inhibitor. The aim of this trial was to evaluate the efficacy and toxicity of erlotinib in Japanese patients with EGFR-wt tumors. METHODS: The primary end point was an objective response. Patients with EGFR-wt tumors previously receiving one to three chemotherapy regimens were enrolled in this trial. The mutation status was assessed using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. Erlotinib was administered (150 mg/d) until disease progression or unacceptable toxicities occurred. RESULTS: Thirty patients were enrolled between January and December 2008. Objective response was observed in one patient (3.3%), and the disease became stable in 18 patients (60.0%). Skin rash was the most common side effect. Grades 3-4 adverse events included pulmonary embolism, keratitis, and anemia. Two other patients developed interstitial lung disease (grades 1 and 2). Nevertheless, all these events were reversible, resulting in no treatment-related deaths. With a median follow-up time of 10.7 months, the median survival time and median progression-free survival times were 9.2 and 2.1 months, respectively. CONCLUSION: This is the first prospective biomarker study showing that erlotinib therapy for pretreated patients with EGFR-wt tumors seems to have a modest activity with no irreversible toxicity.

Centrally located squamous cell carcinoma of the lung mimicking endobronchial tuberculosis.

Here we report a case of centrally located squamous cell carcinoma of the lung mimicking endobronchial tuberculosis. On the basis of the white light bronchoscopic (WLB) findings, bronchial tuberculosis was initially suspected. But transbronchial biopsy of the lesion revealed squamous cell carcinoma. Autofluorescence imaging bronchovideoscopy (AFI) showed the lesion area as magenta. After four cycles of chemotherapy, the magenta area was markedly shrunk on AFI. Performance of AFI might be useful for differentiating centrally located lung cancer from endobronchial tuberculosis.