Background/Aim: To evaluate the outcome of definitive salvage radiotherapy (RT) in non-small cell lung cancer (NSCLC) patients with oligo-recurrence in regional lymph nodes after surgery. Patients ...and Methods: Between January 2003 and December 2016, 33 patients with NSCLC were reviewed from radiotherapy database at our hospital. All patients received photon or proton salvage RT for metastases in the regional lymph nodes. Results: The median follow-up from salvage RT was 35.2 (range=5.9-89.6) months. Recurrences occurred in 18 (55%) patients, and the 3-year overall and progression-free survival rates were 63.8% and 45.1%, respectively. Regional and local control improved patients’ survival and these control rates were increased by use of concurrent chemotherapy (p=0.039) and proton RT (p=0.084). No grade 4 acute or late non-hematologic toxicities were observed. Conclusion: Salvage RT is an effective treatment for NSCLC patients with oligo-recurrence at regional lymph nodes.
Abstract Introduction Among the mutations of epidermal growth factor receptor ( EGFR ), deletions in exon 19 (DEL), and point mutations in exon 21 (L858R) predict the response to EGFR-tyrosine kinase ...inhibitors (TKIs) in primary lung adenocarcinoma. The ability to detecting such mutations using immunohistochemistry (IHC) would be advantageous. Methods The molecular-based and IHC-based EGFR mutations were analyzed in 577 lung adenocarcinomas using high resolution melting analysis (HRMA) and 2 mutation-specific antibodies, respectively. Results In the molecular-based analyses, DEL was detected in 135 cases (23%), and L858R was detected in 172 cases (30%). In the IHC-based analyses, a positive reaction was detected in 59 cases (10%) for the DEL-specific antibody, and in 139 cases (24%) for the L858R-specific antibody. With the molecular-based results set as the gold standard, the sensitivity and specificity of the DEL-specific antibody were 42.2% and 99.5%, respectively, while the sensitivity and specificity of the L858R-specific antibody were 75.6% and 97.8%, respectively. The antibody specificities improved when the threshold for the mutation-positive reactions was set as >50% of immunopositive tumor cells. The significant predictors of the clinical response to EGFR-TKI were molecular-based EGFR mutations ( p < 0.001) and IHC-based EGFR mutations ( p = 0.001). However, a multivariate analysis revealed that only molecular-based EGFR mutations were significantly correlated with the clinical response ( p < 0.001). Conclusions Mutation-specific antibodies demonstrated extremely high specificities, but their sensitivities were not higher than those of molecular-based analyses. However, IHC should be performed before a molecular-based analysis, because it is more cost-effective and can effectively select candidates for EGFR-TKI therapy.
Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin with an aggressive clinical course. Although anthracycline- and platinum-based regimens are empirically used as first-line ...treatments for metastatic or unresectable cases, no salvage therapy has been established. A 73-year-old man with platinum-refractory recurrent MCC was treated with amrubicin. The symptoms improved soon, and a partial response was achieved. A total of nine cycles of amrubicin were administered in nine months with manageable adverse events until disease progression was finally observed. The present findings suggest the potential of amrubicin monotherapy as a second-line therapy for patients with advanced/recurrent MCC.
Cisplatin is administered in combination with massive hydration to avoid renal toxicity, making its administration difficult in an outpatient setting. Although a short hydration protocol for ...cisplatin has been recently developed, its safety is not fully understood.
Consecutive patients with lung or other cancer and an Eastern Cooperative Oncology Group performance status of 0-2 who were receiving chemotherapy containing cisplatin at a dose of ≥60 mg/m(2) in a single administration were evaluated. Seventy-four patients were treated with a short hydration protocol consisting of 1750-2250 ml of hydration with mannitol and magnesium supplementation over a period of 3.75-4.75 h on Day 1. Sixty-nine patients were treated with a conventional hydration protocol consisting of 2100-2600 ml of hydration over 6.5-7.5 h on Day 1 with pre- and post-hydration on Days 0, 2 and 3. Toxicity was then compared between the two groups.
An elevated serum creatinine level ≥grade 1 was significantly less frequent in the group receiving the short hydration protocol than in the group receiving conventional hydration. Other toxicities were similar between the two groups. Consequently, the completion rate for the planned treatment in the short hydration group (73.0%, 54/74) was significantly higher than that in the conventional hydration group (53.6%, 37/69).
Short hydration is safe, making cisplatin-containing chemotherapy easier to perform.
A subset of lung cancers harbors an EML4-ALK (echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase) gene fusion, and detecting this subset may hold therapeutic implications. ...Many prior studies used fluorescence in situ hybridization (FISH) analysis for this detection, but FISH may have disadvantages including signal decay and dark-field examination that may obscure tissue architecture. In this study, we explored the potential of the ALK-break-apart chromogenic in situ hybridization (CISH) method to detect ALK-rearranged lung cancer.
We examined 15 lung adenocarcinomas with reverse-transcriptase polymerase chain reaction-proven EML4-ALK fusion transcripts and 30 ALK-negative cases. One hundred tumor cells were evaluated by CISH and FISH for each case, and a detailed signal profile was recorded and compared.
CISH preserved tissue architecture and cytomorphology considerably and facilitated the signal evaluation using a routine light microscope. Positive rearrangement signals (splits or isolated 3′ signals) were identified in 13 to 78% (mean ± SD, 41% ± 19%) of tumor cells in the ALK-positive cohort and in 0 to 15% (mean ± SD, 6% ± 4%) of cells in the ALK-negative cohort. The two groups were best separated by a cutoff value of 20%, with a sensitivity of 93% and a specificity of 100%. The only false-negative tumor having only 13% CISH-positive cells displayed predominantly (76%) isolated 5′ signals unaccompanied by 3′ signals. FISH showed largely similar signal profiles, and the results were completely concordant with CISH.
We have successfully introduced CISH for diagnosing EML4-ALK-positive lung adenocarcinoma. This method allows simultaneous visualization of genetics and tumor cytomorphology and facilitates the molecular evaluation and could be applicable in clinical practice to detect lung cancer that may be responsive to ALK inhibitors.
Epidermal growth factor receptor (EGFR) mutations, especially deletional mutations in exon 19 (DEL) and L858R, predict gefitinib sensitivity in patients with non-small cell lung cancer (NSCLC). In ...this study, we validated EGFR mutation detection using high-resolution melting analysis (HRMA) and evaluated the associations between EGFR mutations and clinical outcomes in advanced NSCLC patients treated with gefitinib on a larger scale.
The presence of DEL or L858R was evaluated using HRMA and paraffin-embedded tissues and/or cytologic slides from 212 patients. In 66 patients, the results were compared with direct sequencing data.
HRMA using formalin-fixed tissues had a 92% sensitivity and a 100% specificity. The analysis was successfully completed in 207 patients, and DEL or L858R mutations were detected in 85 (41%) patients. The response rate (78% versus 8%), time-to-progression (median, 9.2 versus 1.6 months), and overall survival (median, 21.7 versus 8.7 months) were significantly better in patients with EGFR mutations (P < 0.001). Even among the 34 patients with stable diseases, the time-to-progression was significantly longer in patients with EGFR mutations. Patients with DEL (n = 49) tended to have better outcomes than those with L858R (n = 36); the response rates were 86% and 67%, respectively (P = 0.037), and the median time-to-progression was 10.5 and 7.4 months, respectively (P = 0.11).
HRMA is a precise method for detecting DEL and L858R mutations and is useful for predicting clinical outcomes in patients with advanced NSCLC treated with gefitinib.
The introduction of targeted agents has resulted in a breakthrough in advanced cancer treatment. We propose a new classification for these agents to evaluate them in appropriate clinical trials ...according to agent class. Class I agents that inhibit driver oncogene activities result in massive and rapid tumor shrinkage, with response rates as high as 70% when administered to patients with appropriate targets. These agents can be evaluated in single-arm phase II trials with response rate as the primary endpoint. Class II agents inhibit one oncogene that is partially responsible for accelerating tumor cell proliferation. Their clinical features include synergism with cytotoxic agents and moderate single-agent activity, as shown by response rates of between 10% and 30%. Randomized phase II trials in patients with over-expressed targets are appropriate for the evaluation of these agents. Class III agents inhibit proliferation regulators that are not always oncogenic. Their clinical activity is unique, as they confer a survival benefit on patients with a minimum tumor shrinkage effect. Class IV agents target environmental molecules that act on normal cells surrounding tumor cells, such as the endothelial cells that form vessels. Placebo-controlled randomized phase II trials are required to identify the clinical activities of both class III and IV agents. Class V agents act by enhancing anti-tumor immunity. Immune-related response criteria should aid the evaluation of these agents. We believe that this classification for targeted agents should facilitate their further clinical development.
Background
It is not uncommon for patients with lung cancer to receive supportive care alone. However, the clinical characteristics of these patients have not been fully studied. We conducted a ...retrospective study to identify the clinical characteristics of definitive lung cancer patients treated with supportive care alone.
Methods
We retrospectively analyzed the percentage of and reasons for definitive lung cancer patients treated with supportive care alone at a regional cancer center. We also investigated the histological diagnostic approaches, palliative therapy types, primary treatment locations after hospital consultation, and places of death.
Results
A total of 1,223 patients were histologically diagnosed as having lung cancer between 2011 and 2014. Of these, 160 (13%) patients were treated with supportive care alone. The primary reason for treatment with supportive care alone was a poor performance status (PS) in almost half of the patients. Overall, 40% of the patients received supportive care at home, and 17% were admitted to a palliative care unit (PCU). Death occurred at home for 17% of the patients and in the PCU for 42% of the patients.
Conclusion
This study revealed that 13% of histologically proven lung cancer patients were treated with supportive care alone, mostly because of a poor PS. Only 40% of these patients received home care, suggesting the need for a more accessible home care system for patients and their families.
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