Cancer Immunotherapy is enhanced by a Vitamin D loading dose - Aug 2023

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STUDY: Systematic vitamin D supplementation is associated with improved outcomes and reduced thyroid adverse events in patients with cancer treated with immune checkpoint inhibitors: results from the prospective PROVIDENCE study

Cancer Immunol Immunother . 2023 Nov;72(11):3707-3716. doi: 10.1007/s00262-023-03522-3
Melissa Bersanelli # 1 2, Alessio Cortellini # 3 4, Alessandro Leonetti 1 2, Alessandro Parisi 5, Marcello Tiseo 1 2 6, Paola Bordi 1, Maria Michiara 1, Simona Bui 1, Agnese Cosenza 1, Leonarda Ferri 1, Giulia Claire Giudice 1 6, Irene Testi 1 6, Elena Rapacchi 1, Roberta Camisa 1, Bruno Vincenzi 7, Giuseppe Caruso 1, Antonio Natale Rauti 6, Federica Arturi 6, Marco Tucci 8, Valentina Santo 7, Valentina Ricozzi 7, Vanessa Burtet 9, Paolo Sgargi 10, Renata Todeschini 2, Fable Zustovich 11, Luigia Stefania Stucci 12, Daniele Santini 13, Sebastiano Buti 1 2 6

Wonder why there is an extreme drop off in vitamin D benefit at day/week/month 25
Background: Hypovitaminosis D can have a negative prognostic impact in patients with cancer. Vitamin D has a demonstrated role in T-cell-mediated immune activation. We hypothesized that systematic vitamin D repletion could impact clinical outcomes in patients with cancer receiving immune-checkpoint inhibitors (ICIs).

Methods: We planned a prospective observational study (PROVIDENCE) to assess serum vitamin D levels in patients with advanced cancer receiving ICIs (cohort 1 at treatment initiation, cohort 2 during treatment) and the impact of systematic repletion on survival and toxicity outcomes. In an exploratory analysis, we compared the clinical outcomes of cohort 1 with a control cohort of patients followed at the participating centers who did not receive systematic vitamin D repletion.

Results: Overall, 164 patients were prospectively recruited in the PROVIDENCE study. In cohort 1, consisting of 101 patients with 94.1% hypovitaminosis (≤ 30 ng/ml) at baseline, adequate repletion with cholecalciferol was obtained in 70.1% at the three months re-assessment. Cohort 2 consisted of 63 patients assessed for vitamin D at a median time of 3.7 months since immunotherapy initiation, with no patients having adequate levels (> 30 ng/ml). Even in cohort 2, systematic supplementation led to adequate levels in 77.8% of patients at the three months re-assessment. Compared to a retrospective control group of 238 patients without systematic vitamin D repletion, PROVIDENCE cohort 1 showed longer overall survival (OS, p = 0.013), time to treatment failure (TTF, p = 0.017), and higher disease control rate (DCR, p = 0.016). The Inverse Probability of Treatment Weighing (IPTW) fitted multivariable Cox regression confirmed the significantly

• decreased risk of death (HR 0.55, 95%CI: 0.34-0.90) and
• treatment discontinuation (HR 0.61, 95%CI: 0.40-0.91)

for patients from PROVIDENCE cohort 1 in comparison to the control cohort. In the context of longer treatment exposure, the cumulative incidence of any grade immune-related adverse events (irAEs) was higher in the PROVIDENCE cohort 1 compared to the control cohort. Nevertheless, patients from cohort 1 experienced a significantly decreased risk of all grade thyroid irAEs than the control cohort (OR 0.16, 95%CI: 0.03-0.85).

Conclusion: The PROVIDENCE study suggests the potential positive impact of early systematic vitamin D supplementation on outcomes of patients with advanced cancer receiving ICIs and support adequate repletion as a possible prophylaxis for thyroid irAEs.
 Download the PDF from VitaminDWiki
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  See their reference #18 in VitaminDWiki Large Vitamin D loading doses recomended (Italy, goal 40-60 ng) - 2011

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STUDY: Immunotherapy harnesses the power of the body's immune system to treat cancer - June 2016

Immunotherapy vs. Chemotherapy: What’s the Difference? June 2016

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For which cancers is immunotherapy used? - Asked Chat-GPT Dec 2023

Immunotherapy is used for a variety of cancers, often depending on the specific characteristics of the cancer and the patient's overall health. Some of the types of cancers for which immunotherapy is commonly used include:

1. Melanoma: Immunotherapy is particularly effective for advanced melanoma, including drugs like checkpoint inhibitors.
2. Lung Cancer: Both small cell and non-small cell lung cancers are treated with immunotherapy, especially in later stages.
3. Head and Neck Cancers: Certain head and neck cancers respond well to immunotherapy, often used in conjunction with other treatments.
4. Bladder Cancer: Immunotherapy can be used for bladder cancer, particularly in advanced stages or when other treatments haven’t worked.
5. Kidney Cancer: Renal cell carcinoma, a type of kidney cancer, is often treated with immunotherapy.
6. Hodgkin Lymphoma: This type of lymphoma has shown a good response to immunotherapy drugs.
7. Non-Hodgkin Lymphoma: Certain types of non-Hodgkin lymphoma are treated with immunotherapy.
8. Leukemia: Some forms of leukemia may be treated with immunotherapy, particularly acute lymphoblastic leukemia.
9. Breast Cancer: Immunotherapy is sometimes used for triple-negative breast cancer, a more aggressive form of breast cancer.
10. Prostate Cancer: Immunotherapy is used in certain cases, especially for advanced prostate cancer.
11. Liver Cancer: It can be used for hepatocellular carcinoma, the most common type of liver cancer.
12. Colorectal Cancer: Immunotherapy may be used, especially for cancers that have specific genetic features.

It's important to note that the suitability of immunotherapy for a particular cancer depends on various factors, including the genetic makeup of the tumor, the stage of cancer, and the overall health of the patient. The field of immunotherapy is rapidly evolving, with ongoing research expanding the list of cancers for which these treatments are effective.

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VitaminDWiki – Cancer - After diagnosis category

• Most cancers reduce vitamin D levels
• Most cancer treatments (chemo, radiation) further lower Vitamin D
• Higher levels of vitamin D minimize many side-effects of cancer therapy
• High levels of vitamin D augment many chemotherapies
• High levels of vitamin D augment cancer immunotherapies
• High levels of vitamin D can kill some cancer cells 1,720 items 12/2023
• Some cancers deactivate the vitamin D receptor

Example VitaminDWiki Studies

• Cancer and Vitamin D - many studies
• Easiest way to treat cancer – take Vitamin D – Nov 2022
• Even after a Cancer diagnosis Vitamin D improves survival – meta-analysis Aug 2022
• Vitamin D is synergistic with many Cancer therapies (radiation in this case) – Aug 2021
• Vitamin D prevents and treats cancer in many ways – May 2021
• Cancer patients need more vitamin D, even those who are supplementing – observational study June 2021
• Metastatic Cancer probably reduced by vitamin D - many studies
• Colorectal Cancer treatment aided by omega-3 plus weekly Vitamin D – RCT Sept 2019
• Radiation therapy, used to treat some cancers, causes less damage if use Vitamin D (or Melatonin) – Aug 2022
• Vitamin D is synergistic with many Cancer therapies (radiation in this case) – Aug 2021
• Vitamin D prevents and treats cancer in many ways – May 2021
• Palliative care is helped by Vitamin D - many studies
• 4X less of one chemo needed after vitamin D receptor activation - June 2020

Breast Cancer

• Breast Cancer survivors with high vitamin D were 3.3 X less likely to have metastases – May 2023
• Breast Cancer survival: 44% with just 10,000 IU of vitamin D per week, 33% with placebo – RCT Dec 2023
• Breast cancer recurred twice as often if have less than 20 ng of vitamin D – Dec 2018
• Breast Cancer chemotherapy 2.7 X more likely to be successful if not vitamin D deficient – Dec 2017

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Also suspect better response by study if had used gut-friendly form of Vitamin D

Many cancers are associated with poor gut function ==> less vitamin D adsorbed

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Suspect a better response by study if hadalso given loading doses to those with more than 30 ng of Vitamin D

Many cancers can be fought only when Vitamin D levels are >30 ng
Breast Cancer, for example, needs >80 ng

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28,600 hits in Google Scholar for search of immunotherapy & cancer & "Vitamin D"

Google Scholar Jan 2024

• The impact of vitamin D on cancer: A mini review - June 2023 https://doi.org/10.1016/j.jsbmb.2023.106308 FREE PDF
• Embracing cancer immunotherapy with vital micronutrients - Sept 2021 10.5306/wjco.v12.i9.712 FREE PDF
• Vitamin D: Promises on the Horizon and Challenges Ahead for Fighting Pancreatic Cancer 2021 https://doi.org/10.3390/cancers13112716 FREE PDF
• Vitamin D, autoimmunity and immune-related adverse events of immune checkpoint inhibitors - Jan 2021 https://doi.org/10.1007/s00403-020-02094-x FREE PDF

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VitaminDWiki – Immunity category

275 items in Immunity category

    see also

Virus category listing has 1401 items along with related searches

Overview Influenza and vitamin D
Vitamin D helps both the innate and adaptive immune systems fight COVID-19 – Jan 2022
Vitamin D aids the clearing out of old cells (autophagy) – many studies
600,000 IU of Vitamin D (total) allowed previously weak immune systems to fight off a virus antigen - Nov 2020
Search for treg OR "t-cell" in VitaminDWiki 1440 items as of Jan 2020
228 VitaminDWiki pages contained "infection" in title (June 2024)
Search VitaminDWik for BACTERIA in title 25 items as of Aug 2019
Vitamin D and the Immune System – chapter Aug 2019
7X less risk of influenza if Vitamin D levels higher than 30 ng – Oct 2017
Common cold prevented and treated by Vitamin D, Vitamin C, Zinc, and Echinacea – review April 2018
Vitamin D improves T Cell immunity – RCT Feb 2016
Immune system - great 11-minute animated video - Aug 2021
   Only the brain is more complex, nothing about Vitamin D
18 titles in VitaminDWiki contained INNATE or ADAPTIVE as of Jan 2023
Increasing publications on vitamin D and Infection

52 studies are in both Immunity and Virus categories

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