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The Journal of Clinical Endocrinology... Jun 2024There are limited therapeutic options for patients with recurrent/metastatic anaplastic thyroid carcinoma (ATC), and radioiodine refractory (RAIR) differentiated thyroid...
BACKGROUND
There are limited therapeutic options for patients with recurrent/metastatic anaplastic thyroid carcinoma (ATC), and radioiodine refractory (RAIR) differentiated thyroid carcinoma (DTC) refractory to multi-kinase inhibitors. This multi-center trial evaluated sapanisertib, a next generation oral kinase inhibitor of mTOR complexes 1/2, in ATC and RAIR DTC.
METHODS
A safety run-in phase I was followed by non-randomized phase II trial in ATC, with an exploratory cohort in RAIR DTC. Primary endpoint was proportion of patients with ATC who were without disease progression at 4 months. Safety and survival outcomes were key secondary endpoints.
RESULTS
Forty-six patients (20 ATC; 26 DTC) were enrolled including 40 (18 ATC; 22 DTC) who received recommended phase II dose of 5 mg daily. Eleven percent (2/18, 95% C.I.: 1.4-34.7%) of patients with ATC were progression-free at 4 months, 22.2% (4/18) had stable disease as best response. Enrollment in the ATC cohort stopped early with 18 patients out of proposed 23 due to overall futility. One confirmed partial response (4.5%, 1/22) occurred in RAIR DTC, with stable disease in 63.6% (14/22) patients. Median progression-free survival was 1.6 (95% C.I.: 0.9-2.8) months and 7.8 (2.0-not reached) months in ATC and DTC, respectively. Grade 3 treatment related adverse events occurred in 30% of patients who received the phase II dose, most common being anorexia, nausea, diarrhea, fatigue, skin rash and hyperglycemia. Genomic alterations in the PI3 K/AKT/mTOR pathway were not associated with response or PFS.
CONCLUSIONS
Sapanisertib monotherapy did not meet the primary endpoint of this trial (proportion progression-free at 4 months) in ATC, and did not show clinically meaningfully activity. Clinical trials with alternative therapeutic strategies are needed.
CLINICAL TRIAL REGISTRATION
NCT02244463.
PubMed: 38943664
DOI: 10.1210/clinem/dgae443 -
Japanese Journal of Clinical Oncology Jun 2024Enfortumab vedotin (EV) was approved for patients with metastatic urothelial carcinoma (mUC) who progressed after anticancer therapy on September 2021 in Japan. The...
BACKGROUND
Enfortumab vedotin (EV) was approved for patients with metastatic urothelial carcinoma (mUC) who progressed after anticancer therapy on September 2021 in Japan. The association between the occurrence of EV-related side effects and clinical outcome remains to be elucidated.
METHODS
We identified 97 mUC patients treated with EV therapy at our five institutions from the date of approval to March 2023. The median follow-up period was 7.0 months. We retrospectively analyzed the efficacy and safety of EV.
RESULTS
The median age of the patients was 71 years old, 39% had PS of 1 or more, and 56.7% had primary tumor in upper urinary tract. Overall response rate (ORR) to EV therapy, median progression-free survival (PFS), and overall survival (OS) were 43.3%, 7.52 months, and 12.78 months, respectively. Any grade of treatment-related skin disorder, dysgeusia, peripheral neuropathy, gastrointestinal disorder, and hyperglycemia occurred in 61 (62.9%), 36 (37.1%), 34 (35.1%), 29 (29.9%), and 18 (18.6%) patients, respectively. The patients with EV-associated peripheral neuropathy had significantly higher ORR (58.8% vs. 34.9%, P = .032) and longer median PFS (8.05 vs. 6.31 months, P = .017) and OS (not reached vs. 11.57 months, P = .008, respectively) than those without. The occurrence of peripheral neuropathy after EV treatment and the presence of peritoneal dissemination were factors independently associated with PFS (hazard ratio = 0.46, P = .008 and hazard raito = 3.83, P = .004, respectively) and OS (hazard ratio = 0.30, P = .005 and hazard raito = 4.53, P = .002, respectively).
CONCLUSIONS
The occurrence of EV-related peripheral neuropathy might be associated with the efficacy of EV therapy in mUC patients.
PubMed: 38943559
DOI: 10.1093/jjco/hyae082 -
The American Journal of Dermatopathology Jun 2024Microsecretory adenocarcinoma (MSA) was first described in 2019 as a low-grade salivary gland neoplasm of intraoral origin with distinct histopathologic features and a...
Microsecretory adenocarcinoma (MSA) was first described in 2019 as a low-grade salivary gland neoplasm of intraoral origin with distinct histopathologic features and a characteristic MEF2C::SS18 fusion. Recently, skin was also identified as a primary site for MSA in a report by Bishop et al. Due to its rarity and resemblance to other adnexal tumors, MSA is a challenging diagnosis. Herein, we present a case of cutaneous MSA that was unique for the presence of a significant microcystic component and marked adnexal hyperplasia, which mimicked myxoid microcystic adnexal carcinoma (MAC). A 58-year-old presented with a 1 year history of an enlarging eyelid nodule. Histopathologic analysis revealed dermal tumor composed of small tubules containing inspissated bluish mucinous material. Accompanying marked adnexal hyperplasia and many microcysts were also present. Tumor cells expressed S100 protein, which is distinct from MAC, while p63 immunohistochemistry showed marked loss of myoepithelial labeling, as is common in primary adenocarcinomas. Next generation gene sequencing detected the characteristic MSA fusion protein MEF2c::SS18. We report a novel presentation of MSA that simulated MAC because of the presence of associated microcystic change. The presence of S100 immunopositivity and the identification of MEF2C::SS18 fusion confirmed the diagnosis of cutaneous MSA.
PubMed: 38941552
DOI: 10.1097/DAD.0000000000002788 -
Clinical Cancer Research : An Official... Jun 2024To assess efficacy and safety of apalutamide plus goserelin for androgen receptor (AR)-positive, unresectable or recurrent/metastatic salivary gland carcinoma (URM-SGC).
PURPOSE
To assess efficacy and safety of apalutamide plus goserelin for androgen receptor (AR)-positive, unresectable or recurrent/metastatic salivary gland carcinoma (URM-SGC).
PATIENTS AND METHODS
This was an open-label, single-arm, multicenter phase II study for patients with AR-positive URM-SGC. The primary endpoint was the overall response rate (ORR) by an independent central radiology review (ICRR) in the first 24 response evaluable patients who had been observed at least 24 weeks from study initiation (primary RE patients). The efficacy was to be declared when at least 8 of the 24 primary RE patients responded.
RESULTS
31 patients were enrolled. In the first 24 primary RE patients with a median follow-up of 7.4 months, confirmed ORR by ICRR was 25.0% (6/24 patients; 95%CI: 9.8%-46.7%; P =0.11 (one-sided)), which did not meet the predefined criteria of efficacy. Clinical benefit rate (ORR + rate of stable disease for at least 24 weeks) and median progression-free survival were 50.0% and 7.4 months, respectively. Both median duration of response and overall survival were not reached. Exploratory analyses showed a better ORR of 54.5% (6/11) in patients with AR-positivity ≥ 70% and no history of prior systemic therapy. Grade 3 or higher treatment-emergent adverse events were reported in 35.5% (11/31), which included skin rash, anemia, leukopenia, and cancer pain.
CONCLUSIONS
Although this study did not meet the predefined efficacy criteria, apalutamide plus goserelin showed clinically meaningful efficacy in a subset of patients with AR-positive SGC and safety consistent with prior experience in prostate cancer.
PubMed: 38940667
DOI: 10.1158/1078-0432.CCR-24-0455 -
Cureus May 2024Non-melanoma skin cancers (NMSC) such as basal cell carcinoma (BCC) as well as squamous cell carcinoma (SCC) are the two most common skin malignancies globally. They are...
Non-melanoma skin cancers (NMSC) such as basal cell carcinoma (BCC) as well as squamous cell carcinoma (SCC) are the two most common skin malignancies globally. They are observed more frequently among Caucasians than Asians, and their incidence is inversely proportional to the pigmentation levels. Even though the occurrence of skin cancers in India is lower, the absolute quantity of cases may be considerable due to the vast population. Here, we report five cases of NMSC in people having skin of colour.
PubMed: 38939265
DOI: 10.7759/cureus.61192 -
Journal of Chemotherapy (Florence,... Jun 2024Camrelizumab is an immune checkpoint inhibitor clinically used to treat various types of tumours. In this study, the authors provided the first report of a case of an...
Camrelizumab is an immune checkpoint inhibitor clinically used to treat various types of tumours. In this study, the authors provided the first report of a case of an anaphylactic reaction induced by camrelizumab in the treatment of a patient with squamous cell carcinoma of the floor of the mouth. The patient, a 58-year-old man, was diagnosed with advanced squamous cell carcinoma of the floor of the mouth, with cancer infiltration and multiple metastases. He underwent treatment for nine cycles, in which cycles 1-5 he received camrelizumab, albumin-bound paclitaxel, and cisplatin (200 mg of camrelizumab each time, every 3 weeks), with no adverse reactions; in cycle 6, he received albumin-bound paclitaxel and cisplatin, with no adverse reactions; and in cycles 7-9, he received camrelizumab and albumin-bound paclitaxel. However, 30 min after 8th administration of camrelizumab (cycle 9), he suddenly developed sweating, a pale complexion, clamminess and cyanosis of the limbs (percutaneous arterial oxygen saturation [SpO] = 82%, blood pressure [BP] = 79/49 mmHg, heart rate [HR] = 83 beats/min [bpm] and respiratory rate [RR) = 12 bpm). The patient underwent intravenous infusion of methylprednisolone (80 mg) combined with dopamine to boost the BP; he regained consciousness 20 min later, and many parts of his skin appeared smooth, with no desquamation and accompanied by itching erythema, especially on the upper limbs. Approximately 2 h after treatment, the patient's skin erythema subsided (vital sign monitoring results: SpO = 100%, BP = 122/84 mmHg, HR = 91 bpm and RR = 17 bpm); the patient did not complain about his obvious discomfort. Despite the rarity of acute anaphylactic reactions among immune-related adverse reactions, great importance should be given to anaphylactic reactions of camrelizumab due to its extensive clinical application.
PubMed: 38937985
DOI: 10.1080/1120009X.2024.2372525 -
Skin Research and Technology : Official... Jul 2024Patients with myotonic muscular dystrophy (MMD) were observed to have numerous basal cell carcinoma (BCC) and abnormal dysplastic nevi (DN) on non-sun exposed skin.... (Review)
Review
OBJECTIVE
Patients with myotonic muscular dystrophy (MMD) were observed to have numerous basal cell carcinoma (BCC) and abnormal dysplastic nevi (DN) on non-sun exposed skin. Simultaneously a large study published in the Journal of American Medical Association (JAMA) illustrated that patients with MMD have "overall" an increased risk for cancer development. Based on these findings, this author in 2010 postulated that dysregulation of RNA binding proteins (RBP), responsible for clinical manifestations of MMD, is also responsible for the development of BCC and melanoma.
METHODS
To report new research elucidating the etiology of melanoma, BCC, MMD-induced cancers, and potentially other environmentally induced malignancies.
RESULTS
Dysregulation of RBP induces aberrant mRNA splicing; recent data indicates that abnormal mRNA splicing not just plays a key role in the pathogenesis of melanoma but is a hallmark of essentially all human malignancies.
CONCLUSION
The author's hypothesis is that ultraviolet (UV) radiation induces DNA damage in intronic regions of a variety of genes. Furthermore, these UV-induced abnormal DNA dimers, repeats and mutations interfere with normal mRNA splicing thus producing abnormal proteins. These abnormal proteins in turn activate oncogenic pathways such as hedgehog, MAP kinase, and WNT.
Topics: Humans; Skin Neoplasms; Melanoma; Carcinoma, Basal Cell; Genetic Predisposition to Disease; Genetic Testing; Myotonic Dystrophy; Ultraviolet Rays
PubMed: 38937899
DOI: 10.1111/srt.13832 -
BMC Women's Health Jun 2024Peutz-Jeghers syndrome (PJS) is characterized by the presence of hamartomatous polyps in the gastrointestinal tract and mucocutaneous pigmentation on the lips, oral... (Review)
Review
BACKGROUND
Peutz-Jeghers syndrome (PJS) is characterized by the presence of hamartomatous polyps in the gastrointestinal tract and mucocutaneous pigmentation on the lips, oral mucosa, nose, fingers, and toes. Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) refers to the occurrence of multifocal mucinous lesions in at least two sites, including the cervix, uterus, fallopian tubes, and ovaries, in the female genital tract. SMMN-FGT and PJS are rare diseases with a very low incidence, especially when occurring simultaneously.
CASE PRESENTATION
We report a case in which a woman with a large mass on the left ovary underwent a gynecological surgery and was diagnosed with cervical gastric-type adenocarcinoma and mucinous lesions in the endometrium, bilateral fallopian tubes, and ovary, i.e., SMMN-FGT, by postoperative paraffin pathology. The patient sought medical attention for abdominal distension and enlargement. A gynecological ultrasound revealed a multilocular cystic mass in the pelvis, while serum tumor markers were within normal limits, with mildly elevated carbohydrate antigen 199 and carbohydrate antigen 125 levels. Cervical thin-prep cytology test result was negative. The patient had a family history of PJS with black spots on her skin and mucous membranes since the age of 8 years. She underwent multiple partial small bowel resections and gastrointestinal polypectomy owing to intestinal obstruction and intussusception. She underwent left adnexectomy, hysterectomy, right salpingectomy, greater omental resection, appendectomy and right ovary biopsy, and received six courses of adjuvant chemotherapy with Lopressor plus Carboplatin. Genetic testing revealed a heterozygous serine threonine kinase 11 germline mutation and there were no signs of recurrence during the 18-month follow-up period after treatment.
CONCLUSIONS
This is a rare case in which PJS was complicated by SMMN-FGT. Owing to its extreme rarity, there are no guidelines, but reported cases appear to indicate a poor prognosis. We retrospectively reviewed all cases of collisions between PJS and SMMN-FGT and explored the clinical features, pathological characteristics, diagnosis, treatment methods, and prognosis when the two diseases coexisted. The aim is to deepen the clinicians' understanding of this disease for early detection, diagnosis and treatment.
Topics: Humans; Female; Peutz-Jeghers Syndrome; Metaplasia; Genital Neoplasms, Female; Adenocarcinoma, Mucinous; Ovarian Neoplasms; Adult; Uterine Cervical Neoplasms; Neoplasms, Multiple Primary
PubMed: 38937781
DOI: 10.1186/s12905-024-03184-y -
Archives of Dermatological Research Jun 2024Poor differentiation is strongly associated with poor outcomes in cutaneous squamous cell carcinoma (CSCC). In addition, the National Comprehensive Cancer Network (NCCN)... (Review)
Review
Poor differentiation is strongly associated with poor outcomes in cutaneous squamous cell carcinoma (CSCC). In addition, the National Comprehensive Cancer Network (NCCN) guidelines designate poorly differentiated tumors as "very high risk". Despite its clear prognostic implications, there is no standardized grading system for CSCC differentiation in common use today. CSCC differentiation is graded inconsistently by both dermatopathologists and Mohs surgeons, and reliability studies have demonstrated suboptimal inter- and intra-rater reliability in both of these groups. The absence of a standardized and reliable grading system has impeded the use of differentiation in CSCC staging, despite its apparent correlation with disease outcomes. We performed a comprehensive review of the literature summarizing historical CSCC differentiation grading systems, as well as grading systems in non-cutaneous head and neck SCC as a point of reference. Relevant articles were identified by searching Embase and PubMed, as well as by reviewing reference lists for additional articles and histology textbook excerpts. CSCC grading systems that were identified and summarized include the historical Broders system, the World Health Organization system, the College of American Pathologists' system, and a system described by a 2023 Delphi consensus panel of dermatopathologists.
Topics: Humans; Skin Neoplasms; Carcinoma, Squamous Cell; Neoplasm Grading; Prognosis; Cell Differentiation; Reproducibility of Results; Neoplasm Staging; Skin; Mohs Surgery
PubMed: 38935165
DOI: 10.1007/s00403-024-03184-w -
Head & Neck Jun 2024Reconstruction of skin defects after oncological surgery for a cutaneous squamous cell carcinoma is often mandatory to facilitate adjuvant treatment and/or to prevent...
BACKGROUND
Reconstruction of skin defects after oncological surgery for a cutaneous squamous cell carcinoma is often mandatory to facilitate adjuvant treatment and/or to prevent chronic wound problems. Some of the most challenging regions to reconstruct after resection of a skin tumor are the frontal and parietal parts of the skull.
METHODS
This article describes three patients with large skin defects after oncological surgery that were reconstructed with the use of a (hemi) visor flap.
RESULTS
The (hemi) visor flap is easy to harvest, resulting in a concise procedure and short hospitalization with maximum wound control.
CONCLUSION
The (hemi) visor flap is a safe and reliable option for the closure of large skin defects on the skull. Especially in the older and frail patient group.
PubMed: 38934784
DOI: 10.1002/hed.27854