Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: How to Select the Most Suitable?

Rectal cancer shows specific characteristics in terms of pattern of recurrence, which occurs commonly at both local and distant sites. The standard of care for locally advanced rectal cancer (LARC) including neoadjuvant chemoradiotherapy, followed by surgery based on the total mesorectal excision principles leads to a reduction in the rates of local recurrences to 6-7% at 5 years. However, the outcomes among those with high-risk lesions remain unsatisfactory. On the contrary, neoadjuvant chemoradiotherapy results in long-term morbidities among those with low-risk lesions. Furthermore, the overall survival benefit of neoadjuvant therapy is still a subject to be debated, except for patients with complete or near-complete response to neoadjuvant therapy. Total neoadjuvant therapy (TNT) is a new paradigm of management of high-risk rectal cancer that includes early administration of the most effective systemic therapy either before or after neoadjuvant radiotherapy with or without chemotherapy prior to surgery with or without adjuvant chemotherapy. TNT potentially improves disease-free survival, even though whether it can prolong survival has been debatable. Recently, neoadjuvant chemotherapy only has been proved to be non-inferior to neoadjuvant chemoradiotherapy in patients with low-risk lesions. This review intends to review the current evidences of neoadjuvant therapy and propose a more customized paradigm of management of LARC.

Multi-disciplinary management of esophageal carcinoma: Current practices and future directions.

Esophageal cancer in one of the most malignant and hard-to-treat cancers. Esophageal squamous carcinoma (ESCC) is most common in Asian countries, whereas adenocarcinoma at the esophago-gastric junction (EGJ AC) is more prevalent in the Western countries. Due to differences in both genetic background and response to chemotherapy and radiotherapy, both histologic subtypes need different paradigms of management. Since the landmark CROSS study has demonstrated the superior survival benefit of tri-modality including neoadjuvant chemoradiotherapy prior to esophagectomy, the tri-modality becomes the standard of care; however, it is suitable for a highly-selected patient. Tri-modality should be offered for every ESCC patient, if a patient is fit for surgery with adequate cardiopulmonary reserve, regardless of ages. Definitive chemoradiotherapy remains the best option for a patient who is not a surgical candidate or declines surgery. On the contrary, owing to doubtful benefits of radiotherapy with potentially more toxicities related to radiotherapy in EGJ AC, either neoadjuvant chemotherapy or peri-operative chemotherapy would be more preferable in an EGJ AC patient. In case of very locally advanced disease (cT4b), the proper management is more challenging. Even though, palliative care is the safe option, multi-modality therapy with curative intent like neoadjuvant chemotherapy with conversion surgery may be worthwhile; however, it should be suggested on case-by-case basis.

Polypharmacy and potentially-inappropriate medications are prevalent in the elderly cancer patients receiving systemic cancer therapy and they co-relate with adverse outcomes.

OBJECTIVES: Cancer is the disease of the ageing. Most of the elderly cancer patients have pre-existing illnesses requiring complexity of medical care. Excessive medications would lead not only futility, but also result in adverse outcomes especially if such over-prescription is not appropriate. This study was intended to determine the prevalence of polypharmacy (PP) and potentially-inappropriate medications (PIMs) among elderly cancer patients eligible for active cancer care and their associations with hospitalization and mortality. MATERIALS AND METHODS: This was a prospective cohort study conducted among the elderly non-hematologic cancer patients (≥ 65 years old) whom a medical oncologist had decided suitable for systemic cancer therapy. Demographic data including age, sex, primary site of cancer, cancer stage at diagnosis, Charlson Comorbidity Index (CCI), numbers and kinds of medications used both prior to and during cancer treatment were recorded. Hospitalizations not related to systemic cancer therapy administration and mortality were prospectively monitored. All of the patients had to be followed at least one year after cancer diagnosis. RESULTS: There were 180 eligible participants. Median age in years (IQR) was 68 (65-73). One hundred patients (55.56%) were male and 80 patients (44.44%) were female. Breast (35, 19.44%), lung (31, 17.22%) and colorectal (18, 10%) cancers were the most common diagnoses. Eighty-six patients (47.78%) had metastatic disease at cancer diagnosis. One hundred twenty-two patients (67.78%) had PP (5 or more medications a day) and thirty-six patients (20%) had hyper-PP (10 or more medications a day). One hundred twenty five of the whole cohort (69.4%) had PIMs. Patients with more serious CCI scores were associated with PP and hyper-PP. While patients with primary lung cancer was only the only factor associated with PIMs. When excluding opioids, laxatives and anti-emetics, the most frequently prescribed drugs during cancer treatment, the so-called corrected PP did not associate with worse 1-year survival. Factors correlated with 1-year mortality were more advanced age group (70 years old or more) (OR 2.24; 95% C.I., 1.14-4.41; p = 0.019), primary lung cancer (OR 2.89; 95% C.I., 1.45-5.78; p = 0.003), metastatic disease at cancer diagnosis (OR 4.57; 95% C.I., 1.90-10.97; p = 0.001), and unplanned hospitalizations (OR 3.09; 95% C.I.,1.60-5.99; p = 0.001). While male gender (OR 2.35; 95% C.I., 1.17-4.71; p = 0.016), metastatic stage at cancer diagnosis (OR 2.74; 95% C.I., 1.33-5.66; p = 0.006) and corrected PP (OR 1.90; 95% C.I. 1.01-3.56; p = 0.046) were the significant predictive factors of unplanned hospitalizations. CONCLUSION: Among elderly cancer patients suitable for systemic cancer therapy, around two thirds of patients had PP and PIMs. Higher CCI score was the only significant predictor of PP and hyper-PP; while primary lung cancer was the sole independent factor predicting PIMs. PP was associated with unplanned hospitalizations, albeit not the survival.

Case of renal cell carcinoma associated with synchronous contralateral renal pelvic cancer and bladder cancer.

Synchronous double primary RCC and TCC of the renal pelvis and bladder are extremely uncommon. Proper management is a medical dilemma, and no standard treatment strategy has been agreed upon for this rare situation. Our case involved a large mass in the right kidney and multiple masses in the left renal pelvis, ureter, and bladder. Aggressive management was adopted, including multiagent neoadjuvant chemotherapy, cystectomy and nephroureterectomy, which resulted in an excellent outcome, although our patient will require life-long hemodialysis.

Real-life clinical pattern, management, and survival in Thai patients with early-stage or metastatic triple-negative breast cancer.

OBJECTIVES: To characterize the clinical pattern and evaluate real-life practices in the management of patients with triple-negative breast cancer (TNBC) in Thailand. METHODS: In this multicenter, prospective, observational cohort, females (aged ≥18 years) with histologically and immunohistochemically confirmed TNBC were enrolled. Patient data was collected at four study visits-an inclusion visit (for enrollment), and three subsequent follow-up visits at 12±1, 24±1, and 36±1 months after completion of first day of any planned chemotherapy. RESULTS: Of the 293 enrolled patients, 262 (89.4%) had early-stage TNBC (Stage I: 46 patients, Stage II: 151 patients, and Stage III: 65 patients) and 31 (10.6%) had metastatic TNBC (mTNBC). Chemotherapy was prescribed to 95.4% of the early-stage patients and to 100.0% of the mTNBC patients; most commonly as anthracycline-based in combination with cyclophosphamide and other agents. Patients' performance status and consensus guidelines were the major factors affecting choice of treatment. In early-stage patients, median disease-free survival (DFS) and overall survival (OS) had not been reached for Stage I and II patients, and were calculated to be 37.0 months and 40.0 months, respectively, in Stage III patients. In mTNBC patients, progression-free survival (PFS) and OS were found to be 10.0 months and 14.0 months, respectively. In Stage III patients, anthracycline-based regimens were found to be associated with increase in DFS (p = 0.0181) and OS (p = 0.0027) compared to non-anthracycline-based regimens. In mTNBC patients, non-taxane-based regimens were associated with an increase in PFS (p = 0.0025). The 3-year survival rates in early-stage and mTNBC patients were 85.0% and 21.0%, respectively. CONCLUSION: Clinical management of TNBC in Thailand follows the general guidelines for treatment of TNBC. However, prognosis and survival outcomes are suboptimal, especially in progressive disease. This study is the first assessment in the existing practices in which the results could pave to way to improve the treatment outcome of TNBC in Thailand.

Anaplastic lymphoma kinase (ALK) translocation in paediatric malignant peritoneal mesothelioma: a case report of novel ALK-related tumour spectrum.

AIMS: To report a case of paediatric malignant peritoneal mesothelioma (MPM) with evidence of anaplastic lymphoma kinase (ALK) translocation. METHODS AND RESULTS: We describe a 10-year-old girl who presented with abdominal pain and progressive abdominal distension. She had no history of asbestos exposure. Histopathological, immunohistochemical and ultrastructural analyses were performed and showed a biphasic malignant mesothelioma. In addition, we also studied on a selected set of immunomarkers which may be the potential therapeutic molecular targets including ALK, c-kit (CD117), epidermal growth factor receptor (EGFR) and human epidermal growth factor 2 (HER2)/neu, as well as corresponding molecular analysis. Consequently, we identified ALK expression by immunohistochemistry, together with evidence of ALK translocation by fluorescent in-situ hybridization (FISH) analysis. CONCLUSIONS: Paediatric MPM is associated with ALK translocation in our case. The results may open up a new avenue for the study of molecular genesis of paediatric malignant mesothelioma in the future and help to determine whether patients MMs with ALK translocation would benefit from ALK inhibitor treatment.