Correlation of tumor response and survival in advanced NSCLC patients treated with paclitaxel plus carboplatin (PC) versus paclitaxel plus carboplatin plus gemcitabine (PCG)

7650 Background: We showed that PCG significantly increases both response rate (RR) (43.6% vs 20%) and median survival (10.8 mo vs 8.3 mo) over PC and that at Cox analysis, the only independent prognostic factors were PS and treatment (Paccagnella et al, J Clin Oncol 2006;24: 681–687). According to the Prentice criteria (Stat Med 1989;8: 431–440), to directly relate response and survival it is necessarily that responding patients (and non responding) of both arms have a similar survival and that the survival difference between the two arms disappear when the response factor is included in the multivariate analysis. Methods: Out of 324 pts included in the original analysis, 26 pts were not evaluable for response (early death, toxicity, refusal) before the planned response evaluation at two months and were excluded (15 pts from PC arm and 11 pts from PCG arm). The analysis however was also performed considering the non evaluable patients as non responders. Results: Overall, Responder patients had a median Survival that nearly doubled that of no responders: 14.73 mo vs 7.67 mo (HR: 0.49; CI: 0.31–0.54; P=0.000). No responder pts from PC and PCG arms had a similar survival (median 7.53 mo and 8.07 mo respectively; P= 0.96) as well as responder (CR + PR) patients (median 14.13 mo and 15.40 mo respectively; P=0.38). The principal difference between the two arms was that more than the double of patients in PCG arm responded (43.6% vs 20%) and consequently had a survival advantage of clinical relevance in comparison to patients in PC arm. When tumor response was introduced in the Cox model (as a four level variable), the difference in Overall Survival between PCG and PC changed from a significant level (HR=1.28; CI 1.00–1.63; P=0.049) to a not significant level (HR=0.99; CI: 0.76 - 1.28; P=0.97). Conclusions: To our knowledge this is the first report showing a significant direct correlation between response and survival in advanced NSCLC according to Prentice criteria. No significant financial relationships to disclose.

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Circulating Endothelial Cells for Evaluation of Tumor Response in Non-Small Cell lung cancer patients receiving first-line chemotherapy

The International Journal of Biological Markers ◽

10.5301/jbm.5000154 ◽

2015 ◽

Vol 30 (4) ◽

pp. 374-381

Author(s):

Fadi Najjar ◽

Ghassan Al-Massarani ◽

Israa Banat ◽

Moosheer Alammar

Keyword(s):

Advanced Nsclc ◽

Tumor Response ◽

Small Cell ◽

Percentage Change ◽

Circulating Endothelial Cells ◽

Small Cell Lung ◽

First Line ◽

Significant Difference ◽

Nsclc Patients ◽

Line Chemotherapy

Background Circulating endothelial cells (CECs) reflect the neovascularization in the tumor mass. We therefore investigated the potential role of CEC kinetics after first-line chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Methods Peripheral blood samples were obtained from 45 healthy subjects and 51 naïve patients with advanced NSCLC. Quantification of CD146+ CECs was performed using immunomagnetic separation (IMS). Results Pretreatment and posttreatment CEC levels in NSCLC patients were significantly higher than in healthy subjects (p<0.0001). An objective response was achieved after chemotherapy with partial response (PR) or stable disease (SD) in 26 patients, whereas the remaining 25 patients had progressive disease (PD). Baseline CEC levels were significantly higher in PR/SD patients than in PD patients (p = 0.039). After chemotherapy, CEC count significantly decreased in PR/SD patients (p = 0.014) and increased in patients with PD (p = 0.019). Moreover, there was a significant difference in the percentage change of CEC counts between the 2 groups (p = 0.0016). No significant difference in the median progression-free survival and overall survival (OS) was observed between patients with high baseline CEC counts and those with low baseline CEC levels. However, patients with high percentage change in CEC count had longer OS than those with low percentage change after chemotherapy (p = 0.05). Conclusions Changes in CEC counts after chemotherapy reflect tumor response in advanced NSCLC patients. Moreover, high percentage changes in CEC counts after chemotherapy may predict longer OS in advanced NSCLC. High baseline CEC levels might be an indicator of tumor response in advanced NSCLC patients after first-line chemotherapy.

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Circulating immune-profile as predictor of outcome in advanced NSCLC patients treated with nivolumab.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e14514 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e14514-e14514

Author(s):

Marcello Tiseo ◽

Michele Veneziani ◽

Francesco Gelsomino ◽

Sebastiano Buti ◽

Francesco Facchinetti ◽

...

Keyword(s):

Lymphocyte Subsets ◽

Advanced Nsclc ◽

Tumor Response ◽

Squamous Carcinoma ◽

Absolute Number ◽

Facs Analysis ◽

Small Cell Lung ◽

Cd8 Cells ◽

And Function ◽

Nsclc Patients

e14514 Background: Detection of predictive markers of anti-PD-1/PD-L1 antibodies activity is of pivotal interest in non-small cell lung cancer (NSCLC). This study aimed to identify a circulating immuno-profile as predictor of outcome in NSCLC patients treated with nivolumab Methods: A peripheral blood immuno-profile evaluation was performed at baseline (T0), after 2 (T1) and 4 cycles (T2) of bi-weekly nivolumab in advanced pre-treated NSCLC patients from two Italian Institutions. First tumor assessment was performed after 4 cycles and then every 2 months. FACS analysis of lymphocyte subpopulations [CD3, CD4, CD8, NK (CD56), Treg (FOXP3) and MDSC] was performed. Absolute and % changes of lymphocyte subsets together with their functional and proliferative activity were assessed. Quali-quantitative leucocyte composition at baseline and its variation during therapy were correlated with tumor response and survival. Results: In the overall population of 54 treated patients, baseline Neutrophil-to-Lymphocyte ratio and NK count, lymphocyte count and CD4 variations during therapy showed a statistically significant prognostic role (p < 0.001; p = 0.012; p < 0.001; p = 0.010, respectively). Among 31 patients (squamous carcinoma, n = 17; adenocarcinoma, n = 14) in which all 3 time-points samples were available, 19 were responders (response and stable disease) and 12 non-responders. In responders, absolute numbers of total NK and NKCD56dim subset were higher at baseline and their increase between T0 and T1 was statistically significant (p < 0.05). Responders also displayed increased cytotoxic capability as shown by a higher baseline expression of CD3ζ, perforin and granzyme in NKCD56dim subset. No significant variation was documented in absolute number and functional activity of CD4+ and CD8+ lymphocytes. A higher percentage of CD8+PD-1+ cells at baseline was observed in responders, while non-responders showed a statistically significant increase in the absolute number of MDSC during therapy (p < 0.05). Conclusions: The number and function of NKs and the frequency of PD-1 expression in CD8+ cells could represent predictive peripheral immuno-biomarkers for nivolumab treatment in advanced NSCLC.

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Concurrent and sequential chemoradiation therapy are associated with improved survival among unresected stage III non-small cell lung cancer patients in the United States.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.7043 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 7043-7043

Author(s):

Zhiyuan Zheng ◽

Ramesh Rengan ◽

Jingxuan Zhao ◽

Helmneh M. Sineshaw ◽

Stephen G. Chun ◽

...

Keyword(s):

Median Survival ◽

Stage Iii ◽

Treatment Modalities ◽

Small Cell Lung ◽

Comorbidity Score ◽

Stage Iii Nsclc ◽

Similar Survival ◽

Nsclc Patients ◽

Single Modality

7043 Background: Concurrent chemoradiation therapy (cCRT) has been shown to improve survival outcomes among inoperable stage III non-small cell lung cancer (NSCLC) patients compared to sequential CRT (sCRT) and single-modality therapy in clinical trials. However, many “real world” patients do not receive CRT, and less is known about the survival benefits of concurrent CRT vs other treatment modalities in pragmatic, non-clinical trial settings. Methods: We used the National Cancer Database (2004-2011) to identify unresected stage III NSCLC patients (ages 18-79 years) with Charlson comorbidity score ≤1 and 5-year follow up through the end of 2016. cCRT was defined as the initiations of chemotherapy (CT) and radiation therapy (RT) that were ≤14 days (n = 30,290) apart, whereas sCRT was defined as > 14 days apart (total n = 10,596). The remaining three treatment groups included CT only (n = 11,216), RT only (n = 7,772), and neither CT/RT during first course treatment (n = 10,694). Cox proportional hazard model was used to examine the 5-year survival by treatment modalities, controlling for patient demographics, comorbidity score, health insurance, facility type, area-level social deprivation index (SDI, a composite measure for area-level socio-economic status), driving time to the treatment facility, diagnosis year, and region. Adjusted hazard ratios (HR), and medium survivals were generated by treatment modalities. Results: Among 70,568 unresected stage III NSCLC patients, 61,487 (87.1%) patients died within the 5-year follow-up period. In adjusted analyses, cCRT and sCRT had similar survival (median survivals: 15.3 months), whereas other treatment modalities were associated with worse survival compared to cCRT: CT only (median survival: 10.8 months; HR [95%CI]: 1.46 [1.43-1.50]), RT only (median survival: 6.7 months; HR [95%CI]: 1.93[1.88-1.99]), and no treatment (median survival: 3.2 months; HR [95%CI]: 2.64 [2.58-2.71]), all p < 0.001. Higher comorbidity score (Charlson score 1 vs 0, HR [95%CI]: 1.18 [1.16-1.21]), non-private insurance (Medicaid: 1.16 [1.12-1.20]; Medicare: 1.10 [1.08-1.13]; uninsured: 1.21 [1.16-1.26]) were all associated with worse survival (all p < 0.001). Conclusions: Concurrent CRT and sequential CRT have similar survival outcomes among unresected stage III NSCLC patients with minimum comorbidities, however, single modality and no therapy are associated with much poorer survival among “real world” patients, and should be avoided unless clinically appropriate.

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Comparative Study of Two Thoracic Radiotherapy Schedules for Palliation of Symptom, Radiological Response and Acute Toxicities in Advanced Non-small Cell Lung Cancer

Asian Pacific Journal of Cancer Care ◽

10.31557/apjcc.2021.6.2.159-165 ◽

2021 ◽

Vol 6 (2) ◽

pp. 159-165

Author(s):

Subhash Chand Bairwa ◽

Ravinder Singh Gothwal ◽

Badri Ram ◽

Shivani Gupta ◽

Chetna Meena

Keyword(s):

Advanced Nsclc ◽

Radiation Pneumonitis ◽

Pulmonary Functions ◽

Radiological Response ◽

The Difference ◽

Symptom Palliation ◽

Nsclc Patients ◽

And Control ◽

Fractionation Schedules

Aim: To compare the effect of two RT schedules for thoracic palliation in advanced NSCLC patients (30 Gy in 10 fractions over two weeks and 27 Gy in 6 fractions over three weeks, 2 fractions per week) on pulmonary symptoms, radiological response of the primary thoracic tumour, pulmonary functions and acute toxicities. Material and method: A hospital based quantitative prospective follow-up study. Total 104 advanced NSCLC patients were randomized into two fractionation arms. Evaluation was done pretreatment and 4 weeks after end of RT. Symptoms palliation and radiological response to RT & radiation pneumonitis were assessed by using RTOG 4-point scale and Revised (RECIST) guideline version 1.1 respectively. Radiotherapy was given by Cobalt-60 teletherapy machine. Results: Total 96 patients were evaluated for symptom palliation, radiological response and acute toxicities. The percentage of patients achieving symptom palliation was slightly higher in the control arm. At 1st month of follow-up, 16.67% & 18.75% patients in Study & control arm showed PR. Post-RT mean FVC and FEV1 showed a tendency for improvement in both mean FVC and FEV1 in compare to baseline. Treatment was well tolerated both arms. Grade I nausea and vomiting developed in 43% and 37.5% patients in Study and Control Arm respectively. 58% & 39% patients developed Grade 1 radiation pneumonitis as cough & dyspnea in study and control arms respectively. Grade 2 radiation pneumonitis was developed in 2 patient of study arm at 3rd week of follow-up but they lost follow up. Around 31% patients developed Grade1 esophagitis as dysphagia in both arms at 1 week of follow-up which was reduced up to 7% by 2nd week. A very few patients developed grade1 skin reaction as dermatitis in 1st week of treatment. The difference in symptom palliation, radiological response, pulmonary functions and acute toxicities in both arms was not statistically significant. Conclusion: The two RT fractionation schedules showed equal efficacy in terms of symptoms palliation, radiological response of the primary thoracic tumor, pulmonary functions and acute toxicities. Thus the 27 Gy/6 fractionation arm appears preferable compared to 30 Gy/10 arm to minimize the patients’ visits and load on the machines.

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Chemotherapy of Advanced Non-Hodgkin Lymphomas: A Report of 35 Cases

Tumori Journal ◽

10.1177/030089168206800407 ◽

1982 ◽

Vol 68 (4) ◽

pp. 307-311

Author(s):

Gualtiero Büchi ◽

Umberto Mazza ◽

Clara Camaschella ◽

Giuseppe Saglio ◽

Giovanna Rege Cambrin ◽

...

Keyword(s):

Complete Remission ◽

Median Survival ◽

Combination Chemotherapy ◽

Tumor Response ◽

Stage Iii ◽

Chop Regimen ◽

The Difference ◽

Histologic Types ◽

Total Remission

Thirty-five patients with stage III and IV non-Hodgkin lymphomas, classified according to Lennert have been treated by combination chemotherapy (CVP). Total remission (complete plus partial) was obtained in 68.5% of the cases and complete remission in 28.5%; 73% of the favorable types and 55% of the unfavorable histologic types achieved tumor response: the difference was not statistically significant, perhaps because of the limited number of cases. Median survival was 14 months for the unfavorable histologic types and 28 months for the favorable types; longer survivals were obtained in patients who achieved complete remission. CHOP regimen after CVP in patients refractory to this type of treatment was not satisfactory in our patients.

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