Prognóza

Cases without treatment

• Median survival has been reported to be 2–4 months
• Need to propose treatment to improve the health-related quality of life and overall survival

• Development of early metastasis
• By the time we see patients is that the majority of are in the late stage of disease
• Even for limited-stage, the median survival is around 15 to 30 months
• The 5-year survival is around 10% to 13%
• Extensive-stage
• This goes down to a median survival of around 8 to 13 months
• The 5-year survival is just 1% to 2%
• www.targetedonc.com/view/lessons-from-real-world-cases-of-small-cell-lung-cancer

Desetileté přežití

• ar.iiarjournals.org/content/anticanres/24/3B/2097.full.pdf

-until recently, conventional cancer treatments

-- generally cytotoxic not only to tumor cells

-- broad damage of the cells surrounding the tumor leads to cancer progression and metastasis

-novel approach to optimizing therapy for tumor microenvironments is necessary

• www.jkom.org/journal/view.php?number=4920

• Small cell lung cancer (SCLC, 15% of all cases)
• Non-small cell lung cancer (NSCLC, 85% of all cases)
• Surgery is not beneficial for a limited stage
• Systemic chemotherapy combined with chest irradiation is strongly recommended
• Most patients die from recurrent disease in spite of the dramatic initial response to the chemotherapy and radiation
• www.jkom.org/journal/view.php?number=4920

Apparent Surgical Cure for Metastatic Small Cell Lung Cancer

• Limited stage small cell lung cancer in 1997
• With possible abnormality in left adrenal gland at that time
• Received seven courses of chemotherapy with cisplatin plus etoposide
• Achieved a clinical complete remission.
• Patient did not receive any radiotherapy or prophylactic cranial irradiation for his disease.
• He remained progression free until 5 years later
• In 2002 he developed significant fatigue and iron deficiency anemia with a hemoglobin of 5 g/dl.
• A colonoscopy revealed a poorly differentiated adenocarcinoma of the cecum.
• Subsequent staging abdominal computed tomography scan revealed an 8-cm left adrenal mass
• Biopsied and read as metastatic small cell lung cancer.
• Referred to surgical oncologist and underwent right hemicolectomy as well as simultaneous left adrenalectomy
• Had seven positive lymph nodes from his cecal adenocarcinoma.
• Resected adrenal mass confirmed metastatic small cell lung cancer
• Patient's postoperative course was marked with slow recovery
• Forego any consideration for adjuvant chemotherapy for either his stage III cecal carcinoma or his small cell lung cancer.
• no evidence of progressive disease
• With normal history and physicals, complete blood counts, chest x-ray, and colonoscopy, 64 months after his adrenalectomy
• He has had no further problems from his resected small cell lung cancer
• Remains continuously disease-free 64+ months from his adrenal metastatic resection
• Remains disease free from his colon cancer after resection.
• This case represents the first long-term survival with resection of a metastatic lesion in SCLC
• www.jto.org/article/S1556-0864(15)31498-2/fulltext

Stimulace dalších mutací a poškození DNA

• Chromosomal abnormalities in SCLC are the main reason for the formation of highly heterogeneous tumor cell populations.
• Most notable feature of the SCLC genome is the instability of frequently replicated chromosomes
• Leads to extensive DNA damage
• Copy number variations (CNVs)

Poznámka:

• Instability - to by mohlo souviset s aktivací retrotranspozomů a mohlo by tím pádem na sražení stemness nádoru fungovat antivirotikum na HIV aj.

• Chromosomal losses (3p, 4q, 5q, 10q, 13q, and 17p)
• Gains (3q, 5p, 6p, 8q, 17q, 19, and 20q)
• The most common abnormalities in the SCLC genome

Inhibice

• Gained chromosomal regions contain several oncogenes such as
• myelocytomatosis (MYC) proto-oncogene
• MYCL
• MYCN
• apoptosis regulator B-Cell Leukemia /Lymphoma 2 (BCL2)

Stimulace IFN gamma (pokud něco z té cesty zyblo)

• Copy number loss of IFN-gamma pathway genes
• Associated with deficient T cell infiltration
• Leading to the cold TIME and resistance to ICIs

Stimulace - pokud někde zbylo něco

• Lost chromosomal regions include multiple tumor suppressor genes
• Tumor protein 53 (TP53),
• Retinoblastoma 1 (RB1),
• Phosphatase
• Tensin homolog (PTEN)

• Gene mutations are also significant features of SCLC.
• High incidence of SCLC mutations include:
• TP53, RB1, Neurogenic locus notch homolog protein 2 (NOTCH), MYC, and PTEN.
• Profoundly affect various aspects of tumor cell proliferation, apoptosis, and metabolism
• www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext