Immunotherapy in Lung Cancer: From a Minor God to the Olympus

2020 ◽  
pp. 69-92 ◽  
Author(s):  
Alessandro Russo ◽  
Michael G. McCusker ◽  
Katherine A. Scilla ◽  
Katherine E. Arensmeyer ◽  
Ranee Mehra ◽  
...  
Keyword(s):  
Lung Cancer ◽  
A Minor

scholarly journals Digital Pathology and PD-L1 Testing in Non Small Cell Lung Cancer: A Workshop Record

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1800 ◽  
Author(s):  
Fabio Pagni ◽  
Umberto Malapelle ◽  
Claudio Doglioni ◽  
Gabriella Fontanini ◽  
Filippo Fraggetta ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Gold Standard ◽  
Digital Pathology ◽  
Small Cell ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Standard Quality ◽  
A Minor

A meeting among expert pathologists was held in 2019 in Rome to verify the results of the previous harmonization efforts on the PD-L1 immunohistochemical testing by scoring a representative series of non-small cell lung cancer (NSCLC) digital slides. The current paper shows the results of this digital experimental meeting and the expertise achieved by the community of Italian pathologists. PD-L1 protein expression was determined using tumor proportion score (TPS), i.e., the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. The gold standard was defined as the final PD-L1 score formulated by a panel of seven lung committed pathologists. PD-L1 status was clustered in three categories, namely negative (TPS < 1), low (TPS 1–49%), and high (TPS ≥ 50%). In 23 cases (71.9%) PD-L1 staining was performed using the companion diagnostic 22C3 pharmDx kit on Dako Autostainer, while in nine (28.1%) cases it was performed using the SP263 Ventana kit on BenchMark platform. A complete PD-L1 scoring agreement between the panel of experts and the participants was reached in 57.1% of cases, whereas a minor disagreement in 16.1% of cases was recorded. Italian pathologists performed best in strong positive cases (i.e., tumor proportion score TPS > 50%), whereas only 10.8% of disagreement with the gold standard was observed, and 55.6% regarded a single challenging case. The worst performance was achieved in the negative cases, with 32.0% disagreement. A significant difference resulted from the analysis of the data separated by the different clones used: 22.3% and 38.1% disagreement (p = 0.01) was found in the group of cases analyzed by 22C3 and SP263 antibody clones, respectively. In conclusion, this workshop record proposed the application of a digital pathology platform to share controversial cases in educational meetings as an alternative possibility for improving the interpretation and reporting of specific histological tools. Due to the crucial role of PD-L1 TPS for the selection of patients for immunotherapy, the identification of unconventional approaches as virtual slides to focus experiences and give more detailed practical verifications of the standard quality reached may be a considerable option.

scholarly journals Presence of Epidermal Growth Factor Receptor Gene T790M Mutation as a Minor Clone in Non–Small Cell Lung Cancer

2006 ◽  
Vol 66 (16) ◽  
pp. 7854-7858 ◽  
Author(s):  
Michio Inukai ◽  
Shinichi Toyooka ◽  
Sachio Ito ◽  
Hiroaki Asano ◽  
Shuji Ichihara ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Receptor Gene ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Epidermal Growth ◽  
A Minor

Phase I trial of tirapazamine in combination with cisplatin in a single dose every 3 weeks in patients with solid tumors.

1997 ◽  
Vol 15 (2) ◽  
pp. 773-780 ◽  
Author(s):  
C A Johnson ◽  
D Kilpatrick ◽  
R von Roemeling ◽  
C Langer ◽  
M A Graham ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Performance Status ◽  
Single Agent ◽  
Maximum Plasma ◽  
Time Curve ◽  
Minor Response ◽  
Heavily Pretreated ◽  
Previously Treated ◽  
A Minor

PURPOSE AND METHODS Tirapazamine (SR4233, WIN 59075) is a benzotriazine-di-N-oxide bioreductive agent that is selectively activated to a reactive DNA-damaging species in hypoxic tumors. Preclinical studies show that synergistic antitumor activity results from a schedule-dependent interaction between tirapazamine and several cytotoxic drug classes, including cisplatin. In a phase I combination study, tirapazamine (130 to 260 mg/m2) was administered as a 1-hour intravenous (IV) infusion beginning 3 hours before cisplatin (75 to 100 mg/m2). Thirteen patients received 41 courses of therapy. These patients had an excellent performance status and were not heavily pretreated. The predominant diagnosis was lung cancer. RESULTS The major acute side effects were nausea and vomiting, which were controlled with an intensive antiemetic regimen. Other acute effects included diarrhea and muscle cramping, while with repeated dosing, anorexia and fatigue predominated. Full doses of each agent were well tolerated in combination, although in this previously treated population, fatigue increased markedly after three cycles of therapy. Partial responses were observed in two patients (one with non-small-cell lung cancer and one with breast cancer), and a minor response occurred in a patient with mesothelioma. Tirapazamine pharmacokinetics were linear with respect to increasing dose with a mean maximum plasma concentration (Cmax) of 5.97 +/- 2.25 microg/mL and an area under the concentration-time curve (AUC) of 811.4 +/- 311.9 microg/mL.min at 260 mg/m2. These results are consistent with other ongoing single-agent and combination studies and indicate that therapeutically relevant levels of tirapazamine are achievable in patients based on animal models. The mean cisplatin AUC was 285.6 +/- 46.4 microg/mL.min with mean Cmax values of 3.38 +/- 0.43 microg/mL at 75 mg/m2. The clearance of cisplatin was unaffected by coadministration with tirapazamine. CONCLUSION This trial shows that in previously treated patients, full doses of cisplatin are well tolerated with increasing doses of tirapazamine up to 260 mg/m2. The observation of clinical responses in this trial supports the phase II investigation of this regimen.

scholarly journals Immunotherapy: is a minor god yet in the pantheon of treatments for lung cancer?

2014 ◽  
Vol 14 (10) ◽  
pp. 1173-1187 ◽  
Author(s):  
Christian Rolfo ◽  
Giovanni Sortino ◽  
Evelien Smits ◽  
Francesco Passiglia ◽  
Giuseppe Bronte ◽  
...  
Keyword(s):  
Lung Cancer ◽  
A Minor

scholarly journals Mediastinoscopy: safety and utility Cervical mediastinoscopy: assessing mediastinal lymphadenopathy at Manmohan Cardio-thoracic Vascular and Transplant center

2016 ◽  
Vol 19 (2) ◽  
pp. 7-9
Author(s):  
Bibhusal Thapa
Keyword(s):  
Lung Cancer ◽  
Surgical Site Infection ◽  
Retrospective Analysis ◽  
Mediastinal Lymphadenopathy ◽  
Initial Experience ◽  
Site Infection ◽  
Transplant Center ◽  
Postoperative Diagnosis ◽  
A Minor

Introduction: Mediastinoscopy is considered essential in staging of lung cancer and evaluation of mediastinal lymphadenopathy and masses. This facility has only recently been available at our center. We review our initial experience and analyse its safety and utility in our setting. Methods: Retrospective analysis of data of all patients who underwent cervical mediastinoscopy at Manmohan Cardio-thoracic Vascular and Transplant Center (MCVTC) was done. Demographic, clinical and perioperative data were recorded. Concordance of pre and post-operative diagnosis was studied. Results: Between January 2012 and April 2014, 24 patients underwent mediastinoscopy. The age ranged from 28-75 years (mean = 43.12 ± 15.14). Females outnumbered males (M: F = 3:5). Mediastinoscopy was done for staging of lung cancer in six patients and for assessment of mediastinal lymphadenopathy in 18 patients. One patient had a minor preoperative bleeding. One patient developed surgical site infection. The post-operative stay ranged from 1-4 days (mean = 2.15 ± 0.75). Concordance of pre and postoperative diagnosis was seen in 14 (58%) patients. Amongst the five patients pre-operatively thought to have tubercular mediastinal lymphadenopathy; Tuberculosis was confirmed in only three. Only one of six patients in whom mediastinoscopy was done as a staging procedure in lung cancer was found to have malignant spread in the sampled nodes. Conclusion: Mediastinoscopy is safe and efficacious in diagnosing mediastinal lymphadenopathy. It should be routinely considered in staging of NSCLC and evaluation of enlarged mediastinal nodes.  

Altered Fractionation Radiotherapy in Lung Cancer

1998 ◽  
Vol 84 (2) ◽  
pp. 171-175
Author(s):  
Mauro Palazzi ◽  
Annamaria Cerrotta ◽  
Sergio Villa
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Minor Role ◽  
Small Cell Lung ◽  
Altered Fractionation ◽  
A Minor ◽  
Nsclc Patients

Clinical trials on altered fractionation radiotherapy (RT) regimens currently play a significant role in lung cancer, due to the importance of local control and to the disappointing therapeutic results in this disease. In non-small-cell lung cancer (NSCLC) two strategies are being actively investigated: hyperfractionation with a “curative” aim, and hypofractionation with a palliative aim; in small-cell lung cancer (SCLC) altered fractionation seems to play a minor role at this moment. In this review paper the results of reported randomised trials are summarised and discussed. Conclusions may indicate that through hyperfractionation, particularly if accelerated, clinical outcome of non-metastatic NSCLC patients can be improved; data are however not sufficiently mature to advise its use outside controlled clinical trials. In the palliative setting, hypofractionation should be considered standard treatment.

Talc Pleural Poudrage in the Treatment of Recurrent Neoplastic Effusions

1973 ◽  
Vol 59 (4) ◽  
pp. 287-293 ◽  
Author(s):  
Giorgio Pizzocaro ◽  
Gian Luigi Ravasi ◽  
Federico Bozzetti ◽  
Maurizio Vaglini ◽  
Gaudenzio La Monica
Keyword(s):  
Lung Cancer ◽  
Complete Remission ◽  
Median Survival ◽  
National Cancer Institute ◽  
Pleural Effusions ◽  
Minor Degree ◽  
A Minor ◽  
Talc Poudrage

Between 1966 and 1970, 23 talc pleural poudrages for neoplastic effusions were performed in 22 patients at the National Cancer Institute in Milan. No recurrence was observed in 16 cases and in another 2 the effusion recurred to a minor degree. Talc poudrage was ineffective in 2 patients and 3 died postoperatively. The median survival of the patients who had a complete remission of their pleural effusions was 8 months, with minimum of 2 months and maximum of 2 years. The best results were obtained in patients with pleural mesotheliomas or pleural metastatic carcinomas other than lung cancer. Talc pleural poudrage seemed to be more effective when performed early in patients not yet in the preterminal phase.

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