Impact of COVID-19 pandemic on psychological wellbeing of Oncology clinicians in the Middle East and North Africa (MENA) region.

OBJECTIVE: The reorganization of cancer services and the increased work burden on health care providers during the COVID-19 pandemic are likely to be associated with significant negative psychological impact. The aim of this study is to evaluate the impact of COVID-19 pandemic on the psychological well-being of oncology clinicians in the Middle East and North Africa (MENA) region. MATERIALS AND METHODS: We randomly invited 1500 oncology clinicians including medical oncologists, clinical oncologists, radiation oncologists and surgical oncologists from 17 countries in the MENA region to complete a web-based survey to determine the level of psychological stress during the COVID-19 pandemic from October 2020 to January 2021. The questionnaire was based on the Perceived Stress Scale (PSS), Generalized Anxiety Disorders Scale (GAD-7) and WHO Well-being Index (WHO-5). The data was analyzed using SPSS version 21 and the difference between groups was measured by t-test and ANOVA. RESULTS: Overall, 520 (35%) clinicians including 368 (71%) males and 152 (29%) females participated in the survey with 247 (47%) participants between the ages of 36 to 45 years. Average score of 29.6 for males and 30.2 on PSS-10, indicative of high-perceived stress in both the genders. Compared to males, females had significantly higher anxiety levels on GAD-7 scale (p=.04), but this difference in stress level and well-being was not observed on PSS-10 (p=.134) and WHO -5 well-being index (p=.709). Clinicians of age 25-35 years had significantly higher anxiety levels on GAD-7 scale (p=.004) and higher stress on PSS (p=.000) as compared to other age groups. Age over 55 years was associated with lower levels of anxiety and stress on GAD-7 and PSS. Oncology clinicians working in public sector experienced significantly lower stress as compared to private sector on PSS scale (p=.041). CONCLUSIONS: Anxiety and stress levels among oncology clinicians have significantly increased in COVID-19 pandemic in the MENA region. Females and young clinicians had higher anxiety and stress, while oncology clinicians over the age of 55 years and working in the public sector reported less stress and anxiety. The general wellbeing of clinicians was well preserved even in a highly stressful and anxious situation.

Mutations in codons 12 and 13 of K-ras exon 2 in colorectal tumors of Saudi Arabian patients: frequency, clincopathological associations, and clinical outcomes.

Mutations in codons 12/13 of K-ras exon 2 are associated with reduced benefit from anti-epidermal growth factor receptor antibody treatment for metastatic colorectal cancer (CRC). Here, we evaluated the frequency of K-ras mutations and their relationship with clinicopathological features and treatment outcomes in Saudi Arabian patients with CRC. The genetic status of K-ras was determined in 300 patients diagnosed with CRC. Clinical information was collected retrospectively. K-ras was wild-type in 58% and mutated in 42% of the tumors. Most mutations were at codon 12 (89%) and were associated with metastasis [odds ratio (OR) = 1.38 (95%CI = 1.14-1.67] and occurrence of >40 µg/L carcinoembryonic antigen (CEA) [OR = 1.33 (1.1-1.74)] during diagnosis. Patients in stages I-III of the disease with wild-type K-ras tumors had a median relapse free survival (RFS) of 29 months in contrast to 22 months for those with the mutated K-ras tumor (P = 0.0357). In multivariate analysis, only the stage of the disease significantly predicted RFS (P = 0.001). Patients in stage IV of CRC with the wild-type K-ras tumor did not reach the median overall survival (OS), whereas patients with the mutated K-ras tumor survived for 23.5 months (P = 0.044). CEA level >40 µg/L (P = 0.004) and status of K-ras (P = 0.044) were independent predictors of OS. This is the largest study investigating K-ras mutations in patients with CRC in the Middle East. Mutations were associated with advanced stage of CRC, higher serum CEA, shorter RFS and OS.

Lapatinib-based therapy for women with advanced/metastatic HER2 positive breast cancer.

BACKGROUND: Lapatinib alone or in combination with other agents, mostly capecitabine is used for patients with advanced/metastatic HER2 positive breast cancer (HER2(+)BC) after progression on trastuzumab based therapy. Here we report our experience with lapatinib based therapy in this setting. MATERIAL AND METHODS: 67 consecutive patients received lapatinib based therapy. 58 (86.6%) received lapatinib + capecitabine (LC), 7 (10.4%) with other agents and 2 (3.0%) as single agent lapatinib. Data was collected from patients' records retrospectively. RESULTS: Objective response to lapatinib based therapy in 64 evaluable patients was 64.0% in all patients and 64.0% in patients who received LC. Median progression free survival and overall survival were 10 and 27 months in all patients and 10 and 17 months in patients who received LC, respectively. 16 (24.0%) patients had dose delay > 1 week and/or dose reduction. CONCLUSION: Lapatinib based therapy is an effective treatment for women with advanced/metastatic HER2(+)BC after prior exposure to trastuzumab. It yields meaningful response rates, progression free and overall survival. Some patients require dose adjustments.

Case report and review of literature: temporary asymptomatic sinus bradycardia with carboplatin, paclitaxel and bevacizumab: under-reported in clinical trials and under-disclosed in practice.

INTRODUCTION: Paclitaxel, Carboplatin, and Bevacizumab (PCB) is one of the standard chemotherapy regimens for the treatment of non-small cell lung cancer. Temporary asymptomatic bradycardia is recognized toxicity of paclitaxel. However, it is under-disclosed to patients during consent for treatment and is under-reported in clinical phase III trials. CASE REPORT: Here, we report a case of severe but temporary asymptomatic sinus bradycardia (heart rate 39 bpm) in a patient immediately after receiving PCB. The patient was not informed of this risk during consent to therapy leading to non-compliance with future plan of management. Literature search showed that bradycardia is documented. However, it is not reported adequately in land mark phase III trials' reports. CONCLUSION: The cause of bradycardia in this patient is probably paclitaxel. Oncologists should disclose this potential risk to patients during consent to chemotherapy. Investigators should monitor and report it when conducting land mark trials.

Platinum-based adjuvant chemotherapy for early-stage epithelial ovarian cancer: single or combination chemotherapy?

OBJECTIVE: To evaluate the clinical benefit and toxicity of two regimens; single agent carboplatin (C) and a carboplatin/paclitaxel (CP) combination in early epithelial ovarian cancer. DESIGN: A retrospective review. SETTING: Single cancer centre serving a population of 2.1 million in the northwest of England. POPULATION: All women treated with adjuvant chemotherapy for International Federation of Obstetrics and Gynecology stage Ia-IIc ovarian cancer between 2002 and 2005. METHODS: Case and operation notes were reviewed. Details of the surgery performed, performance status (PS), tumour histology, stage, grade, intended chemotherapy, chemotherapy received, acute and late toxicity, relapse and death were all recorded. MAIN OUTCOME MEASURES: Overall survival (OS), relapse-free survival (RFS), acute and late toxicity. RESULTS: Sixty women received CP and 35 received C. Younger women (P < 0.0001) and those with a better performance status (P = 0.045) were more likely to receive CP. Median follow- up was 38 months (range 0-70). Five-year OS was 62% (95% CI 44-81%) for C and 73% (95% CI 61-85%) for CP P= = 0.316. For the subgroup with stage I disease and good PS (0/1) 5-year OS was 80% (59-100%) for C and 79% (63-95%) for CP; P = 1.0. For those with stage 2 disease, 5-year OS was 29% (95% CI 0-62%) for C and 63% (95% CI 44-82%) for CP; P = 0.025. Subgroup analyses by grade or histology showed no difference in OS. P was discontinued prematurely in nine (15%) women on account of toxicity, whereas C was not stopped early. P-related neuropathy (G1/2) was reported in ten (17%) women at 6 months and in two (3%) at 1 year. CONCLUSIONS: Combination therapy is administered more often than carboplatin; especially in those with younger age, better PS and nonmucinous histology. Recurrence and death rates were similar with both treatments. Well-designed trials are needed to identify the optimum chemotherapy regimen in this group.

A matched case-control study of Triple negative vs. HER-2 positive (irrespective of hormonal status) breast cancer: two subtypes with high risk features and poor outcome.

Genetic profile studies of breast cancer identified a number of biologically different subtypes. These genetic subtypes are often surrogated by estrogen receptors (ER), progesterone receptors (PR) and HER2 status as measured by immunohistochemistry (IHC). Triple negative (TN) subtype is recognized to have high risk features and poor outcome. Over expression of the HER2 is also recognized as a poor outcome marker. The characteristics and outcome of HER2 positive tumours (irrespective of hormonal status) (HER2 HR+/-) identified by IHC have not addressed in the era of surrogate genetic subtyping. Therefore, we retrospectively compared the risk features and clinical outcome of patients with TN against these with HER2 HR+/- tumours.

A matched group study of triple negative versus HER-2 positive (irrespective of hormonal status) breast cancer: two subtypes with high-risk features and poor outcome.

INTRODUCTION: Genetic profile studies of breast cancer identified a number of biologically different subtypes. These genetic subtypes are often surrogated by oestrogen receptors (ERs), progesterone receptors (PR) and HER2 status as measured by immunohistochemistry (IHC). Triple negative (TN) subtype is recognized to have high-risk features and poor outcome. Over-expression of the HER2 is also recognized as poor outcome marker. The characteristics and outcome of HER2 positive tumours (irrespective of hormonal status) (HER2 HR+/-) identified by IHC have not addressed in the era of surrogate genetic subtyping. Therefore, we retrospectively compared the risk features and clinical outcome of patients with TN against these with HER2 HR+/- tumours. PATIENTS AND METHODS: Forty patients with HER2 HR+/- tumours were matched for age and stage to 40 patients with TN tumours. Clinical and pathological data were collected retrospectively. All patients were managed in a single institution. RESULTS: Tumour grade and stage and rate of pathologically involved lymph nodes were similar in both groups. There was a trend of more lymphovascular invasion in HER2 HR+/- than TN patients (40% vs. 27.5%. p=0.07). Relapse and death rates were not statistically different (p=0.469 and p=1.0, respectively). Median relapse free survival was 38 months for TN and not reached for HER2 HR+/- patients (Log rank; p=0.757). Median overall survival was not reached in both groups. Multivariate analysis did not identify TN or HER2 HR+/- status to have any differential impact on RFS. CONCLUSION: HER2 HR+/- tumours exhibit high risk, presenting features and relatively poor clinical outcome possibly not very different from the increasingly recognized TN tumour.

Serum potassium, calcium and magnesium in patients receiving ESHAP chemotherapy for relapsed lymphomas.

UNLABELLED: Etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) is one of the mostly widely used chemotherapy regimens for patients with relapsed lymphomas. Cisplatin administration is commonly associated with electrolyte imbalance. Careful monitoring of renal function and serum electrolytes is therefore essential in this setting. AIMS: To review the practice of electrolyte monitoring - potassium (K), calcium (Ca) and magnesium (Mg) - in patients receiving ESHAP and the frequency and severity of abnormalities and their management. METHODS: Twenty-one consecutive patients received ESHAP. The medical records of 16 patients were retrievable and reviewed retrospectively. Results of serum K, Ca and Mg were collected prior to and after cycles 1, 2 and 3 of ESHAP, if measured. RESULTS: Serum K levels prior to every cycle did not show any noticeable change. The means were 4.42, 4.34 and 4.43 mmol/l before cycles 1, 2 and 3, respectively. In one patient hypokalaemia was severe, refractory and symptomatic when preceded by hypomagnesaemia. Serum-adjusted calcium levels showed only minimal reduction. The means were 2.46, 2.40 and 2.38 mmol/l before cycles 1, 2 and 3 respectively. Mean serum Mg levels prior to every cycle showed progressive reduction; 0.84, 0.75 and 0.67 mmol/l before cycles 1, 2 and 3, respectively. This was associated with a progressive increase in the amount of required Mg supplementation. Serum K, Ca and Mg was measured prior to 100%, 67% and 35% of administered cycles, respectively. CONCLUSION: In patients receiving ESHAP, hypokalaemia can occasionally be seen, especially if preceded by hypomagnesaemia. Mild cumulative hypocalcaemia is recognised. Hypomagnesaemia is a progressive complication and physicians need be aware of its importance. alcaemia is recognised. Hypomagnesaemia is a progressive complication and physicians need be aware of its importance.

Epirubicin/vinorelbine adjuvant chemotherapy in young women with breast cancer is associated with preservation of menstrual function.

AIMS: To determine whether the epirubicin and vinorelbine regimen in the adjuvant (neoadjuvant) treatment of breast cancer has minimum adverse effects on menstrual function. PATIENTS AND METHODS: Thirty-six premenopausal women with a median age of 32 (25-47) years received epirubicin and vinorelbine. Twenty-eight received only epirubicin and vinorelbine without any other neo/adjuvant chemotherapy agents. Amenorrhoea was defined as absence of periods 6 months after the completion of chemotherapy. The medical records of all patients were reviewed retrospectively. RESULTS: Twenty-six patients were assessable for effects of epirubicin and vinorelbine on menstruation. All the 26 patients resumed menstruation within 6 months of completing epirubicin and vinorelbine treatment. Epirubicin and vinorelbine was well tolerated. After a median follow-up of 38.5 (11-78) months, six (21%) patients had developed disease relapse and three (11%) had died. The 6.5-year disease-free survival and overall survival probabilities were 77 and 86%, respectively. CONCLUSION: Adjuvant (neoadjuvant) epirubicin and vinorelbine is an effective and well-tolerated regimen that is associated with the retention of menstrual function.

Metastatic struma ovarii: late presentation, unusual features and multiple radioactive iodine treatments.

Metastatic malignant struma ovarii is rare and there is a lack of agreement on the criteria of diagnosis and the lines of management. Here we describe a patient with struma ovarii that was initially diagnosed as benign and presented 10 years later with distant metastases. At this time, a pathological review of the initial lesion found that it contained invasive well-differentiated follicular carcinoma. The case was associated with a number of unusual features and challenging management issues, such as a delayed diagnosis of recurrence, functioning metastases with treatment consequences, tumour lysis-induced thyrotoxicosis and cerebrospinal fluid rhinorrhea. The diagnosis and management of struma ovarii should be led by an expert multidisciplinary team. Radioactive iodine should be considered in the management of metastatic disease.

Exemestane in metastatic breast cancer: effective therapy after third-generation non-steroidal aromatase inhibitor failure.

Exemestane is a potent steroidal aromatase inhibitor (AI) with activity in post-menopausal women with metastatic breast cancer, with a reported clinical benefit (CB) rate of 24.3% after prior AI therapy. Data on 114 patients (112 female, 2 male) were obtained retrospectively at two cancer centres. Sixty-five percent of patients were confirmed as oestrogen receptor (ER) positive. All patients had received prior third-generation AI therapy. Responses were seen in 5% and the overall CB rate (CR+PR+SD24 weeks) was 46%. Median PFS and OS were 18 and 61 weeks, respectively. In patients with visceral disease, the CBR was 33%. Patients with known ER-positive disease had a CBR of 47%, and a median TTP of 19 weeks. No benefit was seen in patients with known ER-negative disease. Survival was better in those with CB (median survival not reached in those with CB, 28 weeks in those without CB P<0.0001). Efficacy persisted in those patients who had received 3 prior lines of hormonal therapy, including adjuvant treatment. These data confirm exemestane to be an effective therapy after third-generation non-steroidal AI in post-menopausal ER-positive metastatic breast cancer, including visceral disease.

Phase II study of docetaxel in patients with relapsed or refractory malignant lymphoma.

We report the activity and toxicity of docetaxel in 12 evaluable heavily pretreated patients with relapsed and refractory non-Hodgkin's lymphoma and Hodgkin's disease. In all, 42% achieved a partial response, 25% achieved stable disease. Median duration of response was 16 (10-21) weeks. The median overall survival was 70 (9-178) weeks and for responders it was 120 (22-178) weeks. One patient developed one episode of neutropenic sepsis. Docetaxel has limited activity in this group of patients.

The skeletal metastatic complications of renal cell carcinoma.

Of the 103 patients with advanced renal cell carcinoma 31 (30%) developed symptomatic radiologically confirmed skeletal metastases. These were typically lytic, predominantly affecting the axial skeleton and associated with considerable skeletal morbidity. Solitary bone lesions occurred in 14 (45%) of patients. The median survival of patients with bone metastases was 12 months. Hypercalcaemia was common in patients both with (29%) and without (44%) bone metastases. The number and rate of skeletal related events was similar to that seen from bone metastases from breast cancer. It would therefore be appropriate to evaluate the effectiveness of bisphosphonate treatment for reducing skeletal morbidity in advanced renal cell cancer with bone metastases.

Markers of bone turnover for the management of patients with bone metastases from prostate cancer.

Although increased bone formation is a prominent feature of patients with osteosclerotic metastases from prostate cancer, there is also some evidence for increased bone resorption. The aim of this study was to compare the clinical utility of new bone resorption markers to that of bone formation in patients with bone metastases from prostate cancer before and after bisphosphonate treatment. Thirty-nine patients with prostate cancer and bone metastasis, nine patients with prostate cancer without bone metastases, nine patients with benign prostatic hyperplasia and 355 healthy age-matched men were included. Urinary non-isomerized (alpha CTX) and beta isomerized (beta CTX) type I collagen C-telopeptides (CTX) and a new assay for serum CTX were used to assess bone resorption. Bone formation was determined by serum osteocalcin, serum total (T-ALP) and bone (BAP) alkaline phosphatase and serum type I collagen C-terminal propeptide (PICP). Fourteen patients with bone metastases were also evaluated 15 days after a single injection of the bisphosphonate pamidronate (120 mg). Levels of all bone formation and bone resorption markers were significantly (P < 0.006-0.0001) higher in patients with prostate cancer and bone metastasis than in patients with benign prostatic hyperplasia, patients with prostate cancer without bone metastases and healthy controls. In patients with bone metastases the median was increased by 67% for serum osteocalcin, 128% for T-ALP, 138% for BAP, 79% for PICP, 220% for urinary alpha CTX, 149% for urinary beta CTX and 214% for serum CTX. After bisphosphonate treatment all three resorption markers significantly decreased by an average of 65% (P = 0.001), 71% (P = 0.0010) and 61% (P = 0.0015) for urinary alpha CTX, urinary beta CTX and serum CTX, respectively, whereas no significant change was observed for any bone formation markers. Patients with prostate cancer and bone metastases exhibit a marked increase in bone resorption, which decreases within a few days of treatment with pamidronate. These findings suggest that these new resorption markers may be useful for the management of these patients.

High dose pamidronate: clinical and biochemical effects in metastatic bone disease.

Eighty-six patients with heavily pretreated progressive bone metastases (52 with breast carcinoma, 17 with prostate carcinoma, and 17 others) were included in 2 studies designed to assess the clinical and biochemical effects of a single 120 mg, 2-hour infusion of pamidronate. No other systemic anticancer treatment or radiotherapy were administered. Pamidronate had a significant beneficial effect, with a reduction in a symptom score measuring pain, World Health Organization performance status, and analgesic consumption and improvement in quality of life when compared with a placebo infusion. Symptomatic improvement corresponded with changes in the rate of bone resorption as indicated by the concentrations of pyridinoline crosslinks in the urine. In patients with the highest rates of bone resorption (N-terminal peptide-bound portion of the collagen crosslink or crosslaps excretion > or = twice that of normal) clinical response or normalization of the rate of bone resorption were rarely observed, with all clinical responses occuring in those patients with bone resorption rates of < twice that of normal. Intriguingly, symptomatic response also correlated with a modest (> 10%) fall in tumor marker levels, suggesting a possible effect of bisphosphonates on tumor activity.

[Patients treated for one year with tianeptine. Results at one of the centers of South-Eastern France]. / Patients traités un an par la tianeptine. Présentation des résultats obtenus par l'un des Centres du Sud-Est de la France.

Tianeptine is a new antidepressant with a tricyclic molecular structure. Its main neurochemical effect consists in an increase in serotonine re-uptake. Its efficacy as antidepressant and its good clinical safety have been confirmed in controlled trials against reference drugs. 1,231 patients with a DSM III diagnosis of major depression or dysthymic disorder were included in a long-term trial with tianeptine. 510 patients completed the one-year treatment period. The results of a subgroup of 100 patients treated in one of the centres of south-east France will be presented. 47 of these patients completed the trial. This study allowed to evaluate the therapeutic efficacy as well as the clinical safety of tianeptine during long-term prescription. Patients were treated in an open design after a 4-7 day placebo washout period. Therapeutic effects were assessed by the C.G.I. items (1 and 2), MADRS, HARS and HSCL. For the evaluation of clinical and paraclinical safety, spontaneous complaints of the patients and CGI-3 were documented; body weight, blood pressure and blood chemistry were also measured. Homogeneity between completers and non-completers was tested before statistical analysis of the clinical effects. Results of completers were analyzed using a two-way ANOVA (time x subjects); Newman-Keuls tests were performed in the case of a significant time effect. End-point analysis was used to test the results of the total sample. Patients completing the trial had a mean MADRS baseline score of 32.8. Given high this score, the patients have to be considered genuinely depressed at inclusion.(ABSTRACT TRUNCATED AT 250 WORDS)