Mucinous Differentiation in Colorectal Cancer: A 10-Year Experience Audit at King Faisal Specialist Hospital and Research Centre, Jeddah.

Given that colorectal cancer is one of the leading causes of mortality, mucinous adenocarcinoma is one of the subtypes and is characterized by the presence of mucin-producing tumor cells with mucin components and is more challenging to manage. In Saudi Arabia, it represents approximately 10-15% of all colorectal carcinoma. The main etiological cause of mucinous adenocarcinoma is yet not well understood. The main goal of our study is to discuss the histopathology and the molecular background of mucinous colorectal adenocarcinoma and also to provide an update on its prognosis and therapeutics from recent published literature. It is a retrospective cohort study that was conducted at King Faisal Specialist Hospital, Jeddah, Saudi Arabia. The study included 68 adult patients diagnosed with mucinous colon cancer, who did surgical resection alone or with or without adjuvant chemotherapy following from January 2011 to December 2020. The mucinous subtypes are found more commonly in the proximal colon. In our study, 26 patients (38.2% of the cases) were right-sided and 35 patients (51.5%) were from the left side, but these included the rectum as well and this reflects the higher incidence of diagnosis of rectal cancer in the region. Most tumors were classified as Grade II in 56 patients (82.4%), consistent with the intermediate differentiation status often associated with the mucinous subtypes. The most common symptom at presentation was abdominal pain in 38 patients (55.9%) followed by per rectal bleeding and abdominal mass. The management in our study was in line with the standard established practice and surgical resection as expected was the primary potentially curative approach. Notably of patients presenting with locally advanced rectal cancer, six patients underwent concomitant chemoradiotherapy followed by surgery and four patients had upfront surgery. The duration of the median follow-up was 32 months. At the time of analysis, 30 patients (44.1%) were alive and remained on regular follow-up, 17 patients (25%) had succumbed to the disease, and 21 patients (30.9%) were lost to follow-up. The median overall survival was not reached, and notably, 49 patients (71.6%) remained alive at the four-year mark. Whilst our study contributes to the current understanding of mucinous adenocarcinomas of the colon, further research in molecular profiling and genomic testing and larger clinical trials with tailored treatments is necessary to refine treatment strategies and improve outcomes.

Variants of Human Mucin Genes in Clear Cell Renal Cell Carcinoma and their Potential Prognostic and Predictive Values.

BACKGROUND: There is no reliable prognostic and predictive biomarkers for clear cell renal cell carcinoma (cc-RCC). METHODS: DNA from 47 cc-RCC tissue samples were sequenced using next generation sequencing and a customized gene panel testing for tumor-driver genes including 19 Mucin genes. RESULTS: Distinctive variants in 12 Mucin genes were present in all samples. These genes are: MUC2, MUC3A, MUC4, MUC5AC, MUC5B, MUC6, MUC7, MUC12, MUC16, MUC17, MUC19, and MUC22. The numbers of distinctive and non-distinctive variants were counted for each sample. The median number of variants was 455. High variant number (HVN) (>455) was associated with shorter overall survival compared to low variant number (≤455) [Median 50 months vs. not reached; P=0.041]. In the 11 patients who received anti-angiogenic tyrosine kinase inhibitors (TKIs), HVN was associated with a trend of shorter progression free survival. CONCLUSION: Alterations in Mucin family genes are common in ccRCC. HVN is associated with worse prognosis and may predict decreased benefit from anti-angiogenic TKIs. KEY WORDS: Mucin; Variants; Renal cell carcinoma; Biomarker; Tyrosine kinase inhibitors.

Cardiac function in women receiving dual anti-Her2 antibodies (trastuzumab and pertuzumab) combined with chemotherapy for breast cancer.

BACKGROUND: Chemotherapy regimens containing a combination of anti-Her2 antibodies are effective but can be associated with cardiac toxicity. OBJECTIVES: We evaluate the outcome with a particular focus on the cardiac function of patients with Her2 over-expressed breast cancer receiving Chemotherapy regimens combined with Trastuzumab and Pertuzumab in routine clinical practice settings. DESIGN AND METHODS: The initial cohort of patients who started Chemotherapy regimens in combination with Trastuzumab and Pertuzumab before September 2019 in four cancer units were reviewed retrospectively. All patients had regular measurements of left ventricular ejection fraction by Doppler ultrasound. RESULTS: Sixty-seven patients were identified. Chemotherapy regimens in combination with Trastuzumab and Pertuzumab treatment were administered in the neoadjuvant and palliative settings in 28 (41.8%) and 39 (58.2%) patients, respectively. All patients underwent left ventricular ejection fraction assessment prior to starting Chemotherapy regimens in combination with Trastuzumab and Pertuzumab treatment and at 3 and 6 months later. Subsequently, left ventricular ejection fraction was measured at 9, 12, 15, 18, 21, and 24 months as long as patients are still receiving any of the treatment components. Compared to baseline, the mean left ventricular ejection fraction was not significantly different at any of the subsequent time points (range; decrease by 0.936% to increase by 1.087%: T-test P value not statistically significant for all comparisons). Trastuzumab and Pertuzumab administration was withheld temporarily for two patients due to clinically suspected cardiac toxicity which was excluded upon further investigations. In the neoadjuvant cohort, 82.3% of patients were relapse free at 3 years. The median progression-free survival was 20 months, and the median overall survival was 41 months in the palliative cohort. CONCLUSION: In this cohort describing our limited initial experience, dual anti-Her2 antibodies (Trastuzumab and Pertuzumab) combined with chemotherapy is effective and not associated with significant cardiac toxicity when the left ventricular ejection fraction is measured every 3 months. This may suggest that previous concerns about cardiotoxicity may have been overemphasized. Further studies investigating less frequent left ventricular ejection fraction monitoring may be warranted.

Biweekly cetuximab in combination with capecitabine and oxaliplatin (XELOX) or irinotecan (XELIRI) in the first-line and second-line treatment of patients with RAS wild-type metastatic colorectal cancer.

Background: Oral capecitabine in combination with intravenous oxaliplatin (XELOX) or irinotecan (XELIRI) are acceptable substitutions to fully intravenous regimens. Biweekly (as opposed to weekly) cetuximab is more convenient when combined with biweekly chemotherapy. Here, we report the tolerability and efficacy of biweekly cetuximab in combination with biweekly XELOX or XELIRI in patients with RAS wild-type metastatic colorectal cancer (RAS-WT mCRC). Methods: Clinical data of consecutive patients with mCRC who received biweekly cetuximab (500 mg/m2) in combination with XELOX or XELIRI between January 2009 and May 2019 in the first- or second-line settings was extracted. Dosage of XEL (Capecitabine/XELODA) was 1,000 mg/m2 twice daily for 9 days, plus on day 1 oxaliplatin 85 mg/m2 or irinotecan 180 mg/m2. Treatment dose reduction and delay for ≥7 days was analysed as surrogates for toxicity. Extended RAS testing was performed in the context of this study for patients who received treatment based on limited KRAS-WT genotype. Results: Sixty one patients with RAS-WT mCRC fulfilled the eligibility criteria. XELOX was administered to 26 (42.6%) and XELIRI to 35 (57.4%) of patients. For all patients in the first-line setting, the objective response rate (ORR), median progression free survival (PFS) and median overall survival (OS) were 54%, 8 months and 25 months, respectively. The corresponding outcomes for the subgroup of patients who received first-line XELOX were 68%, 10 months and not reached, respectively. For all patients in the second-line setting, the ORR, PFS and OS were 50%, 7 months and 20 months, respectively. Chemotherapy components dose reduction and delays were observed in 18 (29.5%) and 25 (41%) patients, respectively. The corresponding frequencies for cetuximab were 3 (5%) and 31 (50.8%). Conclusion: Biweekly cetuximab in combination with XELOX or XELIRI is tolerable and effective. The addition of cetuximab to capecitabine and oxaliplatin is associated with favourable outcome.

Impact of granulocyte-colony stimulating factor on docetaxel-induced febrile neutropenia in patients with breast cancer.

BACKGROUND: Febrile neutropenia (FN) is a life-threatening complication of Docetaxel-based chemotherapy regimens (DBRs). Prophylactic granulocyte-colony stimulating factor (G-CSF) can reduce the risk of FN. This study investigated the effect of G-CSF on FN in patients receiving DBRs for breast cancer. METHODS: Patients treated between 2015 and 2017 were identified from the hospital's pharmacy database and their medical records were examined retrospectively. Data from patients' first four cycles of DBR were collected. FN rate, FN associated length of hospital stay (FN-LOS), and chemotherapy dose modification/delay due to FN were compared between patients who did (G-CSF group) or did not (non-GCSF group) receive prophylactic G-CSF. RESULTS: Of the 276 included patients, 83.3% received a DBR as adjuvant or neoadjuvant therapy, and 50% received docetaxel as combination therapy. Prophylactic G-CSF was administered with the first cycle of a DBR in 69.9% of patients who were significantly less likely to experience FN compared to the non-G-CSF group (6.2% vs. 15.7%; odds ratio: 0.36 [95% CI: 0.16-0.82]; p = 0.020). Collectively and after the 4 DBR treatment cycles, FN rate (4.8 vs. 8.5; odds ratio: 0.54 [95% CI: 0.30-0.97]; p = 0.043) and the mean FN-LOS (3.55 vs. 5.28 days; t = -2.22; p = 0.037) were reduced in the G-CSF group. There was no difference in DBR dose delay/reduction between both groups in cycles 2-4. CONCLUSION: In patients receiving DBRs for breast cancer, prophylactic G-CSF significantly reduced both the rate of FN and duration of hospitalization for FN.

Profiling Activins and Follistatin in Colorectal Cancer According to Clinical Stage, Tumour Sidedness and Smad4 Status.

This study explored the roles of activins and follistatin in colorectal cancers. Paired malignant and normal colonic tissues were collected from archived paraffin-embedded (n = 90 patients) alongside fresh (n = 40 patients) specimen cohorts. Activin ß-subunits, follistatin and Smad4 mRNAs and proteins were measured by real-time PCR and immunohistochemistry (IHC). Mature activin-A, -B, -AB and follistatin proteins were measured by ELISA. Cancer tissues having ≤ the 20th percentile of the Smad4 IHC score were considered as low (L-S4) group. The Smad4-intact SW480 and Smad4-null HT29 colon cancer cell lines were treated with activins and follistatin, and cell cycle was analysed by flow cytometry. The cell cycle inducing (CCND1/CCND3) and inhibitory (p21/p27) proteins alongside the survival (survivin/BCL2) and pro-apoptosis (Casp-8/Casp-3) markers were measured by immunofluorescence. Thirty-nine patients had right-sided cancers (30%) and showed higher rates of L-S4 tumours (n = 17; 13.1%) alongside worse clinicopathological characteristics relative to left-sided cancers. The ßA-subunit and activin-A increased, whilst ßB-subunit and activin-AB decreased, in malignant sites and the late-stage cancers revealed the greatest abnormalities. Interestingly, follistatin declined markedly in early-stage malignant tissues, whilst increased significantly in the advanced stages. All activin molecules were comparable between the early stage right- and left-sided tumours, whereas the late-stage right-sided cancers and L-S4 tumours showed more profound deregulations. In vitro, activin-A increased the numbers of the SW480 cells in sub-G1 and G0/G1-phases, whereas reduced the HT29 cell numbers in the sub-G1 phase with simultaneous increases in the G0/G1 and S phases. The p21/p27/Casp-8/Casp-3 proteins escalated, whilst CCND1/CCND3/BCL2/survivin declined in the SW480 cells following activin-A, whereas activin-A only promoted p21 and p27 alongside reduced CCND3 in the HT29 cells. By contrast, activin-AB increased the numbers of SW480 and HT29 cells in Sub-G1 and G0/G1-phases and promoted the anti-cancer and reduced the oncogenic proteins in both cell lines. In conclusion, activins and follistatin displayed stage-dependent dysregulations and were markedly altered during the advanced stages of right-sided and L-S4 cancers. Moreover, the activin-A actions in CRC could be Smad4-dependent, whereas activin-AB may act as a Smad4-independent tumour suppressor protein.

Frequency and clinical characteristics of HER2 over-expressed breast cancer in Saudi Arabia: a retrospective study.

INTRODUCTION: This study aimed to determine the frequency of human epidermal growth factor receptor 2 (HER2) over-expression in newly diagnosed breast cancer (BC) patients in Saudi Arabia and to assess the clinical characteristics and outcomes in patients with HER2-positive disease. METHODS: In the first part of the study, we retrospectively reviewed the pathology records of all patients diagnosed with BC between 2007 and 2013 at 3 hospitals in the largest 3 cities in Saudi Arabia to determine the frequency of HER2 over-expression. In the second part, a representative sample from the patients identified with HER2 over-expressed BC was selected for further investigation. Data collected included demographic and clinical characteristics such as hormone-receptor status, treatment regimens, survival data, response to treatment, and selected adverse events. RESULTS: 1867 BC records were included in the study. HER2 was overexpressed in 559 patients (29.9%); of those, 348 HER2-positive BC patients were included in subsequent analyses. In the sample of HER2-positive BC patients, median age at diagnosis was 46 years, 0.9% were male, 92.5% were Saudi, 42.4% were Hormone Receptor-negative, and 13.1% had stage IV tumors. Most patients (84.2%) underwent curative intent surgery and 71.8% received radiotherapy. Average tumor size was 3.5 ± 2.5 cm and infiltrating ductal carcinoma was the most common pathology (92.9%). As for pharmacological therapy, the most commonly used regimens were Chemotherapy + Trastuzumab combination (79.1%) in neoadjuvant setting, Hormonotherapy alone (56.2%) in adjuvant setting, and Chemotherapy + Targeted therapy combination (64.8%) as palliative treatment. At the last patient evaluation, 36.9% had complete response, while 33.2% had progressive disease. Median overall survival (OS) and progression-free survival (PFS) were not reached in patients on neoadjuvant/adjuvant pharmacotherapy. As for patients on palliative intent pharmacotherapy, median OS and PFS were 64.7 and 29.3 months respectively. CONCLUSION: This study provided updated figures regarding HER2 overexpression in BC in Saudi Arabia: HER2 overexpression rate (29.9%) was within the range reported in previous studies. Patients' demographic and clinical characteristics were also similar to those reported earlier, with a median age at diagnosis of 46 years and one third of patients having locally advanced/metastatic disease at diagnosis.

The clinical significance of routine risk categorization in metastatic renal cell carcinoma and its impact on treatment decision-making: a systematic review.

Aim: To analyze responses to first-line metastatic renal cell carcinoma (mRCC) treatment stratified by risk criteria. Patients & methods: Clinical trials and observational studies of patients aged ≥18 years, published January 2005-May 2019, were identified via Ovid from MEDLINE, EMBASE, the Cochrane Central Trials Register and the Cochrane Database of Systematic Reviews. Data extracted included progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Results: 47/1269 articles met eligibility criteria. Most studies stratified patients by International Metastatic RCC Database Consortium (n = 19) or Memorial Sloan Kettering Cancer Center (n = 21). PFS, OS and ORR varied according to risk group. Conclusion: Pembrolizumab + axitinib, ipilimumab + nivolumab and avelumab + axitinib were most effective across all risk groups. Favorable-risk patients benefit from sunitinib treatment.

Adjuvant Chemotherapy for Patients with Breast Cancer Based on Clinical and Evolving Oncotype DX Criteria.

INTRODUCTION: Oncotype DX assay recurrence score (ODX-RS) cut-off values have recently changed after the publication of the TAILOR-X trial results. We aim to explore decisions for adjuvant chemotherapy (ACT) based on physicians' clinical assessment and the evolving ODX-RS. METHODOLOGY: Patients who underwent ODX testing after curative surgical resection of estrogen receptor positive (ER+), Her2 non-overexpressed (Her2-) and lymph node-negative (LN-) breast cancer (BC) were eligible. Management of these patients was guided by the results of the old ODX-RS-1 (<18, 18-30, and ≥31) risk grouping. For the purpose of this study, treatment decisions were also assumed according to TAILOR-X results (ODX-RS-2). Decisions of 3 medical oncologists on ACT were solicited by blinding them to the RS to investigate concordance with ODXA RS-1 and 2 recommendations. RESULTS: Sixty-six consecutive patients were included. Median age was 50.5 (range: 21-73) years. There was 1 male patient, and 37/65 females (56.9%) were premenopausal. Among the 3 oncologists, recommendations for ACT based on clinical assessment were discrepant in 29 (43.9%) patients. Based on majority consensus (≥2 oncologists), ACT would have been recommended to 22/41 (53.7%) and 22/46 (47.82%) patients with low-risk tumors according to ODX-RS-1 and ODX-RS-2, respectively. Compared to ODX-RS-1, ODX-RS-2 identifies 12% (46 vs. 41) more low-risk patients and 66% (20 vs. 12 patients) more high-risk patients. CONCLUSION: Overtreatment and discrepancies in the management of patients with ER+/Her2-/LN- early BC can be minimized by the implementation of ODX genomic assay. Some differences in ACT recommendations exist between ODX-RS-1 and ODX-RS-2.

Bone modifying agents for patients with bone metastases from breast cancer managed in routine practice setting: Treatment patterns and outcome.

INTRODUCTION: Bone metastases are common in patients with breast cancer and can lead to pain and skeletal-related events. Bone modifying agents are licensed to be used for these patients. We report the treatment patterns and outcome of zoledronic acid and denosumab in routine practice. METHODOLOGY: Women with bone metastases from breast cancer who have started denosumab or zoledronic acid between 2011 and 2016 were eligible. Those with history of bone modifying agent use prior to diagnosis of bone metastases or with switching treatment between zoledronic acid and denosumab were excluded. Details of patients, tumors, bone modifying agent treatment, selected bone modifying agent toxicity, time to skeletal-related event development, and overall survival were collected retrospectively. RESULTS: In total, 163 women were eligible and included in this analysis. Number of skeletal-related events prior to starting bone modifying agents was 0, 1, 2, and 3 in 91 (55.8%), 53 (32.5%), 13 (8%), and 6 (3.7%), respectively. Zoledronic acid was started for 107 (65.6%) and denosumab for 56 (34.4%) patients. The proportion of patients receiving denosumab increased from 23.1 to 54.3% in years 2011 and 2016, respectively. Dose delay, reduction, and discontinuation due to toxicity were reported more frequently in patients receiving zoledronic acid. Denosumab delayed time to first on-treatment skeletal-related event compared with zoledronic acid (hazard ratio, 0.64; 95% CI, 0.41-0.98; log rank P = 0.044). There was no significant difference in median survival (zoledronic acid: 62 and denosumab: 58 months; log rank P = 0.956). CONCLUSION: Denosumab is superior to zoledronic acid in reducing risk of skeletal-related events and in tolerance profile. However, overall survival is similar with both treatments. Our findings mirror those reported in scrutinized environment of landmark clinical trials.

Neuroendocrine tumor of the kidney: Diagnostic challenge and successful therapy.

The management of gastrointestinal and pancreatic (GEP) neuroendocrine tumors (NETs) has evolved over the recent decade. Primary renal NETs are extremely rare as neuroendocrine cells are not recognized in the normal renal parenchyma. We report a case of primary renal NET characterized by the initial diagnostic challenges. Recurrent and metastatic disease was managed along the lines of management of GEP-NETs, leading to prolonged progression-free survival.

OSSMAR: An Observational Study to Describe the Use of Sunitinib in Real-Life Practice for the Treatment of Metastatic Renal Cell Carcinoma.

PURPOSE: Sunitinib offers improved efficacy for patients with metastatic renal cell carcinoma (mRCC). To provide better disease management in the Middle East, we studied its use in mRCC in real-life practice in this region. MATERIAL AND METHODS: Patients diagnosed with mRCC and started on sunitinib between 2006 and 2016 from 10 centers in Africa and the Middle East region were studied in this regional, multicenter, observational, retrospective trial to obtain routine clinical practice data on the usage patterns and outcomes of sunitinib in mRCC in real-life practice. RESULTS: A total of 289 patients were enrolled. Median age at diagnosis was 58.7 years. The patient characteristics were as follows: 73.6% of patients were males; 85.8% had clear-cell renal cell carcinoma (RCC); 97.5% had unilateral RCC; 66.3% had metastatic disease at initial diagnosis; 56.3% received previous treatment for RCC, among which 98.7% had undergone surgery; and 15.2% and 31.4% were classified in the favorable and poor-risk groups (expanded Memorial Sloan Kettering Cancer Center criteria), respectively. On treatment initiation, the mean total sunitinib dose was 48.1 mg, and 87.6% of patients were started on a sunitinib dose of 50 mg. The mean duration of sunitinib treatment was 9.6 months. Overall response rate was 20.8%, with a median duration of 8.2 months. Median time to progression was 5.7 months. Median follow-up time was 7.8 months. By months 12 and 24, 34.3% and 11.4% of patients, respectively, were still alive. Seventy-six patients (60.9%) experienced 314 adverse events. Twenty-three patients (8.0%) experienced 28 serious adverse events. Overall, 83 patients (28.7%) discontinued their sunitinib treatment. CONCLUSION: The results are indicative of the general treatment outcomes of patients with mRCC in the Middle East using sunitinib in routine clinical practice. Reported adverse events are similar to those described in the literature but at lower frequencies.

Evaluation of the Idylla KRAS and NRAS mutation test in colorectal cancer tissue.

INTRODUCTION: The currently approved techniques for RAS mutations testing in colorectal cancer (CRC) tissue are labor-intensive and time consuming. The Idylla technology (IT) is a rapid and fully automated diagnostics system. The primary aim of this study is to compare the Idylla performance against that of conventional techniques (CT). METHODOLOGY: Archival CRC tumor samples from 2 hospitals were tested for KRAS and NRAS mutations using the IT. Results were compared to those obtained earlier by CT performed in accredited laboratories. Unexplained discordant results were verified locally by next generation sequencing (NGS) to ascertain the accuracy of IT. RESULTS: Forty five samples were processed. All samples underwent dual testing (CT & IT) for KRAS mutations. IT identified mutations in 2 samples that were not detected by CT. Primary concordance rate for KRAS was 93.3% and the accuracy rate improved to 100% after verification and explanation of discordant results. Only 18 samples underwent dual testing for NRAS. Primary concordance and accuracy rates for NRAS were 94.4%. The mean time from dispatching the specimen for RAS testing by CT until receipt of results was 12 (7-28) days compared to few hours when IT was used. CONCLUSION: IT provides a quick and reliable mean for RAS testing. In addition, it identifies mutations that are not detected by CT and thus may provide better guidance to treatment choices.

Obesity and outcome of post-menopausal women receiving adjuvant letrozole for breast cancer.

INTRODUCTION: Aromatase enzyme activity is predominant in adipose tissue. This has led to speculation that aromatase activity is elevated in obese women and subsequently decreased the clinical activity of adjuvant aromatase inhibitors (AIs) in women with estrogen receptor positive (ER+) breast cancer (BC). We investigated the effect of obesity on the outcome of this population. PATIENTS AND METHODS: Records of 320 consecutive post-menopausal (PM) women with ER+ BC starting single agent adjuvant letrozole between years 2005 and 2014 were retrospectively reviewed. Tumour and patients characteristic including body mass index (BMI) on the day of starting letrozole were extracted. Endpoints of main interest were: (1) Frequency of obesity; (2) relapse-free survival (RFS) in nonobese (G1; BMI < 30) and obese (G2; BMI ≥ 30) patients. RESULTS: Obesity (BMI: 30-34.99) and morbid obesity (BMI ≥ 35) were present in 105/320 (32.8%) and 115/320 (35.9%) women, respectively. Median follow-up of patients was 49 months; RFS at 5 years (G1: 69% versus G2: 78%) and at 8 years (G1: 69% versus G2: 71%). Median RFS is not reached in both groups (Log rank; P = 0.097). There was no correlation between BMI and RFS (correlation coefficient r = 0.075; P = 0.174). CONCLUSION: In this cohort, more than two-thirds of PM women starting adjuvant AIs are obese. Obesity did not adversely affect the outcome of women on adjuvant letrozole.

Back to life with checkpoint inhibitors in Hodgkin lymphoma.

Cancer can escape the immune system through different mechanisms. One of which is the expression of program death ligand-1 (PD-L1). This ligand binds to programmed cell death 1 receptor on activated T cells, subsequently leading to inhibition of the immune response. Nivolumab is a novel antibody that binds to programmed cell death 1 and prevents such immune tolerance. Several recently published clinical trials confirmed the clinical efficacy of single agent nivolumab in pretreated patients with different cancer types. Publications on nivolumab in Hodgkin lymphoma are very scarce. We report on a 30-year-old man with stage IVB Hodgkin lymphoma, who failed nine lines of treatments including high-dose chemotherapy and autologous stem cell transplantation and brentuximab vedotin. He reached a major response after four cycles of nivolumab and got married. The available literature is being reviewed. Pre-treated Hodgkin lymphoma is amenable to novel immunotherapy. Nivolumab induces clinically meaningful responses with excellent tolerance. The drug enriches our treatment options by reviving the immune system response against cancer. Further clinical studies are needed to determine the effectiveness on a large patients' cohort.

High-dose chemotherapy and peripheral hematopoietic stem cell transplantation in relapsed/refractory Hodgkin's lymphoma.

PURPOSE: High-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) is used to treat patients with relapsed Hodgkin's lymphoma. In this retrospective study we report our experience with patients who underwent HDCT and ASCT. METHODS: All patients ≥15 years old with relapsed/refractory Hodgkin's lymphoma who underwent HDCT and ASCT between June 2001 and December 2013 were included. RESULTS: Fifty-four patients were identified. Median age at transplant was 22 years (range 15-49 years); 26 were men and 28 were women. Forty-eight patients (89%) underwent HDCT and ASCT after achieving a radiological response to salvage chemotherapy. The rate of radiological complete response to salvage chemotherapy was 13% and reached 50% within 3 months of ASCT in assessable patients. After a median follow-up of 25 months, 31 patients (57%) were still alive with no evidence of relapse or progression. Median event-free survival (EFS) was 24 months (95% CI 8.7-39.3) and 3-year EFS was 56%. Median overall survival (OS) was not reached and 3-year OS was 82.5%. Bulky mediastinal disease at relapse, hemoglobin level, and number of salvage regimens did not significantly impact EFS in univariate and multivariate analyses. After transplantation there was a trend towards longer EFS (30 vs. 24 months; p = 0.36) in patients with a longer time from the end of first-line treatment until relapse (≥12 vs. <12 months). The 100-day transplant-related mortality was 5.5%. CONCLUSIONS: HDCT and ASCT for relapsed/refractory Hodgkin's lymphoma is safe. Our findings are consistent with published phase III results. Longer follow-up is warranted.

Neoadjuvant Chemotherapy With Capecitabine Plus Cisplatin in Patients With Locally Advanced Nasopharyngeal Cancer: Case Series Study.

PURPOSE: Capecitabine, an oral fluorouracil (5-FU) derivative, has replaced 5-FU in many chemotherapy regimens used in various GI tract cancers. The experience with capecitabine in nasopharyngeal carcinoma (NPC) is limited. PATIENTS AND METHODS: We report on eight patients with locally advanced NPC treated with neoadjuvant chemotherapy with capecitabine and cisplatin. RESULTS: All eight patients responded well to the chemotherapy combination and achieved complete remission after definitive chemoradiotherapy. No grade 3/4 toxicities were observed. Five patients experienced a relapse after 6, 8, 9, 12, and 17 months. CONCLUSION: In the patients studied, capecitabine (in combination with cisplatin) was a safe and effective substitution for 5-FU for the neoadjuvant treatment of locally advanced NPC. Larger prospective clinical studies are required to confirm these results.

Disclosure of Adverse Cancer News: The Public's Perspective in a Middle Eastern Country.

OBJECTIVES: The disclosure to patients of unfavorable news related to cancer remains a controversial issue in the Middle East. This study investigated the perspective of the public in Saudi Arabia regarding the disclosure of unfavorable cancer-related news. METHODS: A convenience sample of 103 adult noncancer patients attending a family medicine clinic were asked to respond to 9 closed-ended questions. These questions reflected possible adverse news from the time of diagnosis until the end of life. The primary endpoint was an affirmative response (AR) to =7 questions (AR=7) indicating a preference to be informed of the majority (=78%) of adverse situations. RESULTS: One hundred individuals completed the questionnaire. Of these, 56 (56%) were male, and 44 (44%) were female. The median age was 32 years (18-75 years). Different questions were answered affirmatively by 76-99% of the responders. An AR=7 was reported by 83% of the responders. There was no statistically significant correlation between an AR=7 and age, gender or employment status (Chi-squared P values: 0.731, 0.427, and 0.148, respectively). There was a trend towards an AR=7 among those with higher levels of education compared to those with a lower level of education (88% and 73%, respectively, P=0.055). CONCLUSION: The results of this study suggest that the majority of Saudi Arabians prefer to be informed of most of the adverse health-related news if diagnosed with cancer. These results should encourage physicians to keep cancer patients informed of their health-related events unless the patient indicates otherwise.

Complications of bone metastases from malignant melanoma.

INTRODUCTION: Metastatic bone disease (MBD) carries significant morbidity for patients with cancer. MBD from malignant melanoma (MM) is understudied. We examined the characteristics, morbidity, management and outcome of MBD in patients with MM. METHODS: Patients with metastatic MM managed at two referral cancer centres in England were identified. Those with bone metastases (BMs) were selected. Patient and disease characteristics including skeletal related events (SREs) were extracted from medical records. The Kaplan Meier method was used to calculate median survival. RESULTS: Five hundred and eighteen patients with metastatic MM were managed between years 2000 and 2008. Eighty nine (17.2%) patients had BMs and are the subject of this study. Median age at diagnosis was 53 years and 55% were males. BMs were identified at the time of diagnosis of metastatic disease in 68.5% patients. Sixty-six (74.2%) had multiple bone lesions and 80.9% had axial skeleton involvement. One hundred and twenty nine skeletal related events occurred in 59 (66.3%) patients (50 radiotherapy, 28 hypercalcaemia, 20 bone fractures, 18 spinal cord compression and 13 orthopaedic surgery). The annual skeletal morbidity rate was 2.5. Median survival from diagnosis of BMs was 17.3 weeks and was 5.6 weeks from the first episode of hypercalcaemia. CONCLUSION: MBD affects a clinically important proportion (17.2%) of patients with metastatic MM. It carries a substantial morbidity and mortality exceeding that caused by BMs from breast and prostate cancer. These patients should receive the currently licensed bone modifying agents and should be included in clinical trials addressing MBD.