Local, multimodal intralesional therapy renders distant brain metastases susceptible to PD-L1 blockade in a preclinical model of triple-negative breast cancer

Despite recent progress in therapeutic strategies, prognosis of metastatic triple-negative breast cancer (TNBC) remains dismal. Evidence suggests that the induction and activation of tumor-residing conventional type-1 dendritic cells (cDC1s) is critical for the generation of CD8+ T cells that mediate the regression of mammary tumors and potentiate anti-PD-1/PD-L1 therapeutic efficacy. However, it remains unknown whether this strategy is effective against metastatic TNBC, which is poorly responsive to immunotherapy. Here, using a mouse model of TNBC, we established orthotopic mammary tumors and brain metastases, and treated mammary tumors with in situ immunomodulation (ISIM) consisting of intratumoral injections of Flt3L to mobilize cDC1s, local irradiation to induce immunogenic tumor cell death, and TLR3/CD40 stimulation to activate cDC1s. ISIM treatment of the mammary tumor increased circulating T cells with effector phenotypes, and infiltration of CD8+ T cells into the metastatic brain lesions, resulting in delayed progression of brain metastases and improved survival. Furthermore, although anti-PD-L1 therapy alone was ineffective against brain metastases, ISIM overcame resistance to anti-PD-L1 therapy, which rendered these tumor-bearing mice responsive to anti-PD-L1 therapy and further improved survival. Collectively, these results illustrate the therapeutic potential of multimodal intralesional therapy for patients with unresectable and metastatic TNBC.

Contemporary Neoadjuvant Therapies for High-Risk Melanoma: A Systematic Review

Despite advances in adjuvant immuno- and targeted therapies, the risk of relapse for stage III melanoma remains high. With 43 active entries on clinicaltrials.gov (8 July 2020), there is a surge of interest in the role of contemporary therapies in the neoadjuvant setting. We conducted a systematic review of trials performed in the last decade evaluating neoadjuvant targeted, immuno- or intralesional therapy for resectable stage III or IV melanoma. Database searches of Medline, Embase, and the Cochrane Central Register of Controlled Trials were conducted from inception to 13 February 2020. Two reviewers assessed titles, abstracts, and full texts. Trials investigating contemporary neoadjuvant therapies in high-risk melanoma were included. Eight phase II trials (4 randomized and 4 single-arm) involving 450 patients reported on neoadjuvant anti-BRAF/MEK targeted therapy (3), anti-PD-1/CTLA-4 immunotherapy (3), and intralesional therapy (2). The safest and most efficacious regimens were dabrafenib/trametinib and combination ipilimumab (1 mg/kg) + nivolumab (3 mg/kg). Pathologic complete response (pCR) and adverse events were comparable. Ipilimumab + nivolumab exhibited longer RFS. Contemporary neoadjuvant therapies are not only safe, but also demonstrate remarkable pCR and RFS—outcomes which are regarded as meaningful surrogates for long-term survival. Studies defining predictors of pCR, its correlation with oncologic outcomes, and phase III trials comparing neoadjuvant therapy to standard of care will be crucial.

COMPARE TO INTRALESIONAL THERAPY AND PHYTOCHEMICAL BASED SYSTEMIC DRUG THERAPY IN ORAL SUBMUCOUS FIBROSIS-CLINICOPHAMACOLOGICAL STUDY

Introduction: Oral sub-mucous fibrosis (OSMF) is characterized by abnormal collagen deposition. It is a precancerous disorder and transforms into a malignant tumor in 1.5–15% of all cases. Symptoms include submucous fibrosis, ulceration, xerostomia, a burning sensation restricted mouth opening and restricted tongue protrusion followed by oral mucosal blanching and uvla deviation. All of these greatly interfere with patient quality of life. Curcuma longa has been used for thousands of years as a remedy in the traditional Indian and folk medicine for the cure of a large variety of illnesses, such as inflammation, infectious diseases, and gastric, hepatic, and blood disorders. Curcumin is a major isolated polyphenol from the rhizome of turmeric (Curcuma longa). It has a wide range of pharmacological effects such as antioxidant, anti-inflammatory, antimicrobial, antitumor, and hepatoprotective activities. In our study curcumin used in OSMF as a systemic drug therapy and compare with intra-lesional therapy that’s widely used in OSMF Aims and objective: To check the efficacy of systemic drug therapy (curcumin longa) in OSMF, and compare with intra-lesional therapy (Dexamethasone with Hyaluronidase) in OSMF. Material and method 100 patients with clinically proven Oral Submucous Fibrosis were selected for the study and were randomly divided into 2 groups. The first group was treated with weekly Intralesional injection of 4 mg Dexamethasone & 1500 I.U Hyaluronidase and the second group by oral administration of two Curcumin tablets (Turmix 300 mg) per day for 4 months each. Improvement of burning sensation, interincisal distance, tongue protrusion and ulceration was evaluated on a weekly basis and compare to initial visit to end of treatment duration. Statistical analysis and Results: Burning sensation improved in both the groups from early to late stages. Complete Resolution of burning sensation was noted with Turmix early compare to intra-lesional therapy. The mean increase in inter-incisal distance or mouth opening was more compare to systemic drug therapy. The inter-incisal distance improved in both the groups gradually, but not more significant results at systemic drug therapy the end of both therapies. Tongue protrusion showed greater recovery at the end of last stmonth in group 1 when compared with group 2. Conclusion: Turmix is beneficial and effective in reducing burning sensation in early OSMF Patients so we can concluded on the basis of symptomatic relief systemic drug therapy with phyto-chemical based drug given better results compare to intralesional therapy.

Successful Treatment of Multiple Post-Operative Keratoacanthomas with Topical 5-Fluorouracil

Keratoacanthomas (KAs) are fast-growing tumors and can be difficult to distinguish from squamous cell carcinomas (SCCs). Most KAs are sporadic, but KAs may also arise following traumatic procedures. We report the case of a 94-year-old male who developed multiple KAs following surgical excision of an SCC on the right lower extremity. The patient declined additional procedures including biopsy, surgery, or intralesional therapy. He was started on 5% topical FU using a 2 week on, 2 week off regimen for 16 weeks with resolution of disease. No recurrence was noted at 13 months. Topical 5-FU is a conservative, non-invasive treatment for post-traumatic KAs that is particularly suitable in the elderly, in whom the risks and morbidity from surgical or other non-invasive approaches are worth considering.