ABSTRACTS

A case report of a psoriasis flare-up during treatment with an immune-checkpoint inhibitor

Introduction

With the emerging use of immunotherapy, we see an increase in new immune related side-effects. Dermatologic toxicities, like maculopapillary rash and pruritus, are among the most frequent side effects. We report a case of a patient who developed a more infrequent side-effect on immune-checkpoint inhibition.

Case-report

A 62-year old women was diagnosed with a pT3bN1a melanoma of the left thigh (stage IIIc). Adjuvant treatment with Nivolumab (3mg/kg) was initiated. After two cycles of Nivolumab, the patient developed characteristic skin lesions on her lower legs. She was referred to a dermatologist who diagnosed her with psoriasis vulgaris. Local therapy with Betamethasone-Calcipotriol cutaneous foam was applied and Nivolumab was continued. Re-evaluation after 2 weeks showed a regression of the lesions. A thorough anamnesis revealed that the patient had comparable lesions in the past, that were diagnosed as Psoriasis. The history of psoriasis was not mentioned before the start of Nivolumab, due to full recovery after PUVA therapy in the past.

Conclusion

Flare-up of psoriasis is an infrequent side-effect of immune-checkpoint inhibition. The pathogenesis is not clear, but it might involve up-regulation of T-helper cells. This case emphasizes the importance of a thorough anamnesis and a multidisciplinary approach when confronted with immune-related toxicities. These remarks will only become of more importance with the emerging use of immunotherapy. This is highlighted by the growing amount of case reports that are appearing every year in the literature about different types of immune related toxicities.

Case report of myopericarditis in a patient treated with an immune checkpoint inhibitor

Introduction

Treatment with PD(L)-1 blockers, a type of immune checkpoint inhibitors, implies an increase in T-cell toxicity, which carries the risk of harmful immune-related effects in all organs. The reported incidence of cardiotoxicity related with PD(L)-1 blockers is 1%, with half of the cases being fatal. Recently this spectrum of side effects is gaining more attention. We report a case of a patient with myopericarditis during treatment with Pembrolizumab, a PDL-1 antagonist.

Case-report

A 54-year old woman with a stage 4 malignant melanoma presented with acute diffuse chest and back pain at the emergency department. Since 1 month, treatment had been switched from Dabrafenib and Trametinib to Pembrolizumab because of disease progression. At presentation, clinical examination was reassuring, high-sensitive troponin T was mildly elevated but non-evolutive and ECG was normal. The patient was initially sent home from the emergency department – without consultation of an oncologist or cardiologist – but later represented with increased and mainly inspiratory chest pain. Transthoracic echocardiography at 8 hours after initial presentation showed a limited pleural effusion. Also diffuse ST elevation was then apparent on ECG, as typically seen in pericarditis. The patient was admitted and treated with acetylsalicylic acid and IV corticosteroids. Two days after admission, we noted a marked elevation of hs-troponin T, suggestive for myocardial involvement. The patient was asymptomatic at that moment. ST-elevation on ECG and Hs-troponine T decreased during the following week and no symptoms of heart failure or arrhythmia were noted. Cardiac magnetic resonance imaging one week after treatment showed diffuse contrast captation of the pericard and a focal area of myocardial oedema, confirming myopericarditis.

Conclusion

This case report illustrates a mild form of immune checkpoint inhibitor related cardiotoxicity. The case exposes the importance of primary health care workers being informed of possible immunotherapy related side effects, so that early recognition and consultation with specialists is improved. Since the use of immunotherapy is emerging, close cooperation between oncologists and cardiologists is recommended for prevention, treatment and follow-up of patients with (possible) cardiotoxicity.

Successful and durable disease control after treatment by peptide receptor radionuclide therapy in a patient with disseminated insulinoma: a case report

Insulinomas are a rare group of functional neuroendocrine tumours of the pancreas. Most insulinomas are benign and they grow exclusively at their origin within the pancreas, but a minority metastasizes to distant organs, mainly the liver. Insulinomas are characterised by severe hypoglycaemia induced by inappropriately increased circulating plasma insulin levels. Hypoglycaemia may be life threatening in inoperable malignant insulinomas, where there is no consensus for successful treatment.

Here, we describe the case of a 56-year-old woman, diagnosed with a metastatic insulinoma (neuroendocrine grade II, Ki67 at 4%) to the liver who had been treated initially with somatuline (somatostatin analogue) and then with oral capecitabine and temozolomide regimen. The patient presented with life-threatening severe hypoglycaemia requiring continuous glucose infusion. We initiated treatment with peptide receptor radionuclide therapy (PRRT) with the radiolabelled somatostatin analogue Lutetium-177-DOTA0-Tyr3. PRRT treatment is associated with inhibition of insulin release and an anti-proliferative and tumour stabilising effect. The patient received four cycles during one year, with the last cycle administered two years ago. At the time of writing, the patient is in complete clinical and radiological remission.

Long-term clinical follow-up of breast cancer patients treated with photobiomodulation therapy to prevent acute radiodermatitis (Transdermis trial): Preliminary results

Introduction

In the field of oncology, clinical evidence regarding the efficacy of photobiomodulation therapy (PBMT) to prevent and manage acute radiodermatitis (ARD) is expanding considerably. During PBMT, visible and/or (near)-infrared (NIR) light is applied to the affected skin using non-ionizing light sources (i.e. laser or light-emitting diodes (LEDs)). It induces biochemical reactions in the target cells, which ultimately stimulates the wound healing process, and reduces pain and inflammation. Still, many clinicians are concerned whether the application of PBMT in cancer patients is safe. This study evaluated the disease-free survival (DFS) and overall survival (OS) of breast cancer (BC) patients treated with PBMT for ARD.

Methods

A retrospective data analysis of 120 BC patients treated with prophylactic PBMT (n=60; 2x/week, 808-905nm, 4J/cm², 0.168W/cm²) or placebo (n=60) during their radiotherapy (RT) course (25x2Gy, 8x2Gy) at the Limburg Oncology Center (Hasselt, Belgium) between April 2015 and June 2017, was performed (TRANSDERMIS trial). The follow-up of the patients included a clinical evaluation every 6 months and a blood analysis and mammography yearly in the first 5 years after the end of RT. DFS, defined as any sign of disease progression including secondary malignancy (contralateral breast or non-breast cancer), and OS were estimated.

Results

Data from 93 patients was available (PBMT n=46; placebo: n=47) for a survival analysis; 26 patients were followed up in another medical center and one patient file was not accessible. After a median follow-up of 26 months (range: 1-41), a preliminary analysis of the data by the log rank test demonstrated that DFS was not significantly different between the PBMT and placebo group (98% vs. 100%, resp., p=0.323) and OS was equal in both groups (100%). In the PBMT group, one case of contralateral BC was reported.

Conclusion

For the first time, the safety of PBMT in BC patients undergoing RT was investigated. The preliminary results of this study demonstrate no statistical correlation between the application of PBMT and locoregional recurrence, development of secondary tumors, or OS. Although, to validate these results, a follow-up of at least 5 years is recommended in a broader oncologic patient population.

Unexpected timed presentation of dermatomyositis associated with advanced ovarian cancer

A 73-year-old woman with a history of metastatic serous epithelial ovarian cancer presented with a progressive functional decline occurred just during the scheduled fourth cycle of palliative chemotherapy after surgical debulking for stage 3c disease. She reported at first a facial rash alongside a bit of tiredness which later became a severe limb girdle muscle weakness (within a week she became bedridden).

Physical examination showed limb weakness of the elbow flexor, hip flexor and neck extensor, and skin manifestations namely a heliotrope eruption, Gottron’s sign and periungual erythema. A blood test showed an elevated serum CK concentration at 16,027 IU/L, ANA positive (1:1280) for Anti-SSA 52 (RO52) and positive anti-TIF-1γ.

Muscle biopsy showed several atrophic muscle fibers, partly perifascicular suggesting eventual “incomplete/partial” perifascicular atrophy (rare) and without much necrosis; a multifocal Inflammatory (Mono-lymphocytic) infiltrate mainly in perimysium and focally endomysial, and some lipid deposits in many fibers (mainly type 1 fibers). Acid phosphatase showed positive reactivity in perimysial tissue principally. Clinico-pathological depiction was suggestive of immune dermato-myopathy” (1).

Since a severe dysphagia occurred despite 10 days of oral administration methyl-prednisolone at 1mg/Kg/day, the therapy was reinforced by an intravenous pulsed methylprednisolone approach followed by oral prednisolone tapering dose and immunoglobulin 0.4 mg/kg iv for 4 days.

In this patient, DM manifestations appeared while she was showing full metabolic response to her cancer therapy.

Although the presence of anti-TIF-1γ-Ab is known to be associated with paraneoplastic DM, the fact that the appearance of symptoms was concomitant with a good response to chemotherapy raises a semantical problem about the term “paraneoplastic”. However, differently timed presentations of dermatomyositis associated with advanced ovarian cancer had been described (2). This case also illustrates the described association between dysphagia and the presence of anti-TIF-1γ antibody. (3)

We hypothesize that the tumor cytolysis induced by chemotherapy could be behind the appearance of an immune response that caused the appearance of DM in this patient.

New hopes generated by Next-generation Sequencing of rare tumors: a case of a metaplastic carcinoma of the breast with mesenchymal and sacomatoid differentiation

Metaplastic carcinoma (MC) of the breast is usually associated with the triple negative subtype. Recent studies of gene expression have demonstrated the existence of several “molecular” subtypes among the TNBC. According to Lehman and al., six molecular subtypes were identified. These subtypes might have different sensitivity to treatments and different prognosis. Data are very limited and few systemic treatment options are available. Overall the prognosis is usually poor.

We report the case of a 31-year-old woman with de novo metastatic MC to the liver. The histology is in favor of a mesenchymal and sarcomatoid differentiation. The patient was diagnosed during the last two months of her first pregnancy. Soon after the delivery, she was treated with standard weekly Carboplatin-Paclitaxel in combination with atezolizumab (anti-PDL-1) every 3 weeks. PDL-1 was expressed in the tumor and we note the presence for about five percent of Tumor Infiltrating Lymphocytes (TIL). She experienced a complete metabolic response after eight cycles of therapy.

However, soon after the end of chemotherapy and under atezolizumab “maintenance”, the disease progressed with an extension to other sites (bones, nodes, pulmonary). We initiated an anthracyclin-based chemotherapy without tumor response. Currently, she is treated with cyclophosphamide, metothrexate, 5FU, vincristine and prednisone (CMF-VP).

Targeted DNA sequencing performed on a liver biopsy revealed no BRCA mutation but a PI3K-CA mutation (protein H1047R) who is the one of three most frequent pathogenic mutation, causing increased enzymatic kinase activity and increased downstream signalling. A PI3K-CA inhibitor could be a therapeutic option in this patient.

The routine clinical use of molecular TNBC subtypes is not yet validated, however, the use of those categories for the selection of patients for clinical trials is highly recommended.

This case is highly illustrative of the need for a personalized medicine approach in rare breast cancer subtypes which usually types poorly responsive to chemotherapy.

Progression and complications in melanoma after immunotherapy and corticosteroids treatment

Immunotherapy confirm her benefits in melanoma. Checkpoint inhibitors are first-line therapies in advanced melanoma with durable responses, significant improvement in survival, but several immune-related adverse events (irAEs).

We present a case of a women, 61 years old, with metastatic melanoma disease type SMM, Breslow 2,9 mm, Clark IV, no BRAF mutation, on the Ieft thigh with lymph node invasion. 2 years after initial surgery the patient progressed with metastasis in liver, lungs, pleura, bones and subcutaneous tissues of the thoraco-abdominal wall; she received nivolumab as 1^stline immunotherapy without any response and ipilmumab was initiated as 2^ndline treatment. After 9 weeks of treatment she developed an immune hepatitis confirmed by liver biopsy; the immunotherapy was stopped, and the patient underwent corticosteroids treatment with methylprednisolone 32mg once daily in regression doses, without any antimicrobial prophylaxis. After one week of corticosteroids treatment the patient was hospitalized for an important inflammatory syndrome despite an excellent regression of transaminases.

The chest-CT scan showed the lung’s metastasis with no evolution, but right pulmonary infiltrates and left pleural effusion containing malignant cells. She received amoxicillin-clavulanate with a good clinical and biological evolution and corticosteroids were maintained. One month later she was hospitalized for dyspnea and alteration of the general state. The blood tests showed a moderate inflammatory syndrome and a hepatic cholestasis. The chest-CT scan confirmed the progression of lung metastasis and pleural effusion; ground-glass images appeared and an opportunistic infection versus neoplastic lymphangitis was suspected. The endoscopy revealed suspicious endobronchial lesions and biopsies confirmed the metastatic melanoma. The BAL was leucocytes predominant and bacteriologic cultures yielded Staphylococcus aureus and Aspergillus fumigatus.

Immune- mediated hepatitis usually presented like elevation of liver enzymes and is rarely associated with life-threatening hepatic injury. Most patients with grade 3-4 hepatotoxicity respond at corticosteroid treatment. Monitoring for severe immune-mediated hepatitis is recommended although acute liver failure remains rare. The case illustrates the toxicity of ipilimumab in advanced metastatic melanoma, the complications related to the use of corticosteroids as 1st-line treatment of irAEs and raise the question of using antimicrobial prophylaxis in this precise clinical context.