Kana Watanabe

Re-biopsy status among non-small cell lung cancer patients in Japan: A retrospective study.

OBJECTIVE Disease progression because of acquired resistance is common in advanced or metastatic epidermal growth factor receptor (EGFR)-mutation positive non-small cell lung cancer (NSCLC), despite initial response to EGFR-tyrosine kinase inhibitors (TKIs). In Japan, transbronchial tissue biopsy is the most common sampling method used for re-biopsy to identify patients eligible for treatment. We aimed to investigate the success rate of re-biopsy and re-biopsy status of patients with advanced or metastatic NSCLC completing first-line EGFR-TKI therapy. PATIENTS AND METHODS This was a retrospective, multi-center, Japanese study. The target patients in the study were EGFR mutation-positive NSCLC patients. The primary endpoint was the success rate (number of cases in which tumor cells were detected/total number of re-biopsies performed×100). Secondary endpoints included differences between the status of the first biopsy and that of the re-biopsy in the same patient population, and the details of cases in which re-biopsy could not be carried out. Re-biopsy-associated complications were also assessed. RESULTS Overall, 395 patients were evaluated (median age 63 years), with adenocarcinoma being the most common tumor type. Re-biopsy was successful in 314 patients (79.5%). Compared with the sampling method at first biopsy, at re-biopsy, the surgical resection rate increased from 1.8% to 7.8%, and percutaneous tissue biopsy increased from 7.6% to 29.1%, suggesting the difficulty of performing re-biopsy. Approximately half of the patients had T790M mutations, which involved a Del19 mutation in 55.6% of patients and an L858R mutation in 43.0%. Twenty-three patients (5.8%) had re-biopsy- associated complications, most commonly pneumothorax. CONCLUSIONS Success rate for re-biopsy in this study was approximately 80%. Our study sheds light on the re-biopsy status after disease progression in patients with advanced or metastatic NSCLC. This information is important to improve the selection of patients who may benefit from third-generation TKIs.

Randomized phase II trial of uracil/tegafur and cisplatin versus vinorelbine and cisplatin with concurrent thoracic radiotherapy for locally advanced unresectable stage III non-small-cell lung cancer: NJLCG 0601.

INTRODUCTION The optimal chemotherapy with thoracic radiotherapy (TRT) for locally advanced non-small-cell lung cancer (NSCLC) remains to be established. This randomized phase II study of concurrent chemoradiotherapy was conducted to compare uracil/tegafur (UFT) and cisplatin with vinorelbine and cisplatin for stage III NSCLC. PATIENTS AND METHODS Patients with unresectable stage III NSCLC were randomized to receive UP (400 mg/m(2) UFT on days 1-14 and 29-42 and 80 mg/m(2) cisplatin on days 8 and 36) or NP (20 mg/m(2) vinorelbine on days 1, 8, 29, and 36 and 80 mg/m(2) cisplatin on days 1 and 29). TRT began on day 1 (total 60 Gy in 30 fractions). RESULTS Of 70 enrolled patients, 66 were evaluable for efficacy and safety. The overall response rates were 80% (95% CI: 67-93%) and 71% (95% CI: 55-87%) for the UP arm and the NP arm. With a median follow-up of 20.2 months, the progression-free survival and median survival time were 8.8 and 26.9 months in the UP arm, and 6.8 and 21.7 months in the NP arm. The 2-/3-year survival rates were 51.0/34.3% and 46.9/33.4% for the UP arm and the NP arm, respectively. Grade 3/4 neutropenia occurred in 20% and 58% of patients in the UP and NP arms, respectively. CONCLUSION Combined with concurrent TRT, the UP arm achieved better efficacy and safety compared with the NP arm, suggesting it to be a promising candidate as a standard regimen for locally advanced NSCLC. Further evaluation of the UP arm is warranted.

Subcutaneous cellular neurothekeoma: a pseudosarcomatous tumour

Sir, Topical 5-aminolaevulinic acid (5-ALA) photodynamic therapy (PDT) has become an effective treatment option in dermatology. We report a 70-year-old man who presented with extensive erythematous patches on his abdomen and infiltrated plaques on his arms and neck. These were preceded by extensive figurate and annular erythema on his trunk and limbs for 10 years. He had a history of congestive cardiac failure, atrial fibrillation and chronic obstructive airway disease. Mycosis fungoides (MF) was confirmed histopathologically and he cleared with a course of oral 8-methoxypsoralen (8-MOP) plus ultraviolet A (PUVA). During the next year his MF progressed in extent and he also developed a solitary tumour (1 ́5 1 ́5 cm) on his left posterior thigh. The extensive patch and plaque MF cleared with a further course of oral 8-MOP PUVA, but the nodule remained and became ulcerated and painful over the next 3 months. Biopsy of this tumour showed an ulcerated epidermis with replacement of the subcutaneous tissue by a dense infiltrate of malignant CD31 T cells (Fig. 1a). There was no lymphadenopathy or organomegaly. Blood investigations were normal. Computed tomographic scans of the thorax and abdomen were negative. The tumour was treated with 5-ALA PDT: 5-ALA 20% in a cream base (Aladerm, Crawford Pharmaceuticals, Milton Keynes, U.K.) was applied, under polythene occlusion, to the tumour. Four hours later, excess 5-ALA was wiped off and fluorescence was graded as satisfactory using Woods light. He received 20 J cm at 20 mW cm using a Waldmann PDT lamp (MSR 1200; 580±740 nm). Irradiance was measured using a calibrated handheld meter (International Light 1400A and Selo33/F/W/QND52 detector with spectral shaping and neutral density filters calibrated by D.Taylor, Gloucester, U.K.). He graded pain during treatment as 8/10 but experienced no other adverse effects. The lesion cleared after five consecutive treatments over 12 weeks. Repeat biopsy showed a lymphohistocytic infiltrate but complete clearing of the original infiltrate of malignant T cells (Fig. 1b). During his course of PDT his generalized patch and plaque MF relapsed. The tumour site has remained clear on clinical examination 1 years later. He has required two courses of PUVA therapy for generalized patch and plaque MF during this period. Topical 5-ALA PDT has been proven to be effective for superficial cutaneous cancers, but there are few reports of its use in treating MF. Shanler et al. treated patch/ plaque-stage cutaneous T-cell lymphoma and showed that protoporphyrin IX accumulated within lymphocytic infiltrates; early therapeutic results were promising. Boehncke et al. using an argon laser at 630 nm showed inhibition of proliferation of malignant transformed T cells in vitro and in vivo. Wolf et al. have demonstrated the efficacy of PDT (20% 5-ALA) using a broad-spectrum source (40 J cm at 44 mW cm) in two patients with MF who cleared after four and five PDT treatments, respectively. However, Amman and Hunziker reported a poor response for an infiltrated plaque of MF to just one PDT treatment using an identical regimen. This suggests that multiple treatments are required to obtain a complete histological response. We have demonstrated the benefits of low light dose, low dose rate topical 5-ALA PDT for nodular MF, but a formal study is needed to confirm our findings.

Primary pulmonary synovial sarcoma – transbronchial needle aspiration is a diagnostic approach: a case report with cytological features

The patient was a 68-year-old man in whom a nodular mass was discovered in the lower lobe of the left lung, measuring approximately 1.5 cm at its maximum diameter on a routine chest-X ray. Although the clinical impression was suspicious for malignancy, no abnormalities were found in the punch biopsy and brushing cytology during bronchoscopy. Seven months after the first examination, computed tomography revealed an enlarged pulmonary nodule measuring 3.0 cm at its maximum diameter. Bronchoscopy was then carried out again and transbronchial needle aspiration (TBNA) was carried out.

Alternate-day Treatment with Crizotinib for Drug-induced Esophagitis and Liver Damage in a Patient with EML4-ALK Fusion Gene-positive Lung Adenocarcinoma

A 44-year-old woman who was diagnosed with anaplastic lymphoma kinase-positive lung adenocarcinoma developed brain metastases, multiple spinal metastases and meningeal dissemination. Crizotinib was administered after the failure of first-line chemotherapy. Esophagitis and liver damage were induced by the twice-daily administration of crizotinib at 250 mg and 200 mg, respectively. The alternate-day administration of crizotinib (250 mg, twice daily) was able to control disease progression without any adverse effects for several months. We evaluated the relationship between the serum concentration of crizotinib and the development of esophagitis and liver damage. The alternate-day administration of crizotinib is one of the strategies for managing the severe toxicity of crizotinib.