Lost in Transition? Thoughts on Retirement,Part 2. “Should I Stay or Should I Go Now?”

Although it is accepted that oncologists should plan for a future beyond full-time oncology, there is little practical guidance for a successful transition into retirement. Previously, we provided strategies for various aspects of retirement planning. However, this became significantly more complicated as we face newer issues such as the COVID-19 pandemic, the move to virtual patient care, greater awareness of burnout, and the increasing burden of regulatory issues such as the electronic medical record. It is evident that more prospective information is needed to guide oncologists in planning their retirement.     

“Partner”, “Caregiver”, or “Co-Survivor”—Might the Label We Give the Partners of Cancer Patients Affect the Health Outcome of the Patients and Their Partners?

Having a life partner significantly extends survival for most cancer patients. The label given to the partners of cancer patients may, however, influence the health of not just the patients but their partners. “Caregiver” is an increasingly common label for the partners of patients, but it carries an implicit burden. Referring to partners as “caregivers” may be detrimental to the partnerships, as it implies that the individuals are no longer able to be co-supportive. Recognizing this, there has been some effort to relabel cancer dyads as “co-survivors”. However, many cancer patients are not comfortable being called a “survivor”, and the same may apply to their partners. Cancer survivorship, we argue, could be enhanced by helping keep the bond between patients and their partners strong. This includes educating patients and partners about diverse coping strategies that individuals use when facing challenges to their health and wellbeing. We suggest that preemptive couples’ counselling in cancer centers may benefit both patients and their partners.     

Clinical Implications of “Atypia” on Biopsy: Possible Precursor to Lung Cancer?

Background: It is common for biopsies of concerning pulmonary nodules to result in cytologic “atypia” on biopsy, which may represent a benign response or a false negative finding. This investigation evaluated time to diagnosis and factors which may predict an ultimate diagnosis of lung cancer in these patients with atypia cytology on lung nodule biopsy. Methods: This retrospective study included patients of the Stony Brook Lung Cancer Evaluation Center who had a biopsy baseline diagnosis of atypia between 2010 and 2020 and were either diagnosed with cancer or remained disease free by the end of the observation period. Cox Proportional Hazard (CPH) Models were used to assess factor effects on outcomes. Results: Among 106 patients with an initial diagnosis of atypia, 80 (75%) were diagnosed with lung cancer. Of those, over three-quarters were diagnosed within 6 months. The CPH models indicated that PET positivity (SUV ≥ 2.5) (HR = 1.74 (1.03, 2.94)), nodule size > 3.5 cm (HR = 2.83, 95% CI (1.47, 5.45)) and the presence of mixed ground glass opacities (HR = 2.15 (1.05, 4.43)) significantly increased risk of lung cancer. Conclusion: Given the high conversion rate to cancer within 6 months, at least tight monitoring, if not repeat biopsy may be warranted during this time period for patients diagnosed with atypia.     

Is Direct Laryngoscopy Obsolete? “Trans Nasal Oesophagoscopy” the Complete Endoscopic Solution in Head Neck Practice

Direct laryngoscopy (DL) is the standard of care for the evaluation of suspicious lesions in the larynx and hypo pharynx but requires general anaesthesia and a dedicated operation theatre. While DL offers us the ability to map the lesion adequately and take a biopsy, it requires workup for anaesthesia well as rigid oesophagoscopy for assessing the oesophagus with its associated complications. Sixty-nine patients underwent TNE under topical anaesthesia. The lesions were mapped and biopsies taken. Those patients who had an inadequate evaluation on TNE or negative biopsy underwent direct laryngoscopy. Completeness of evaluation, adequacy of biopsy, presence of synchronous oesophageal lesions and the modified Gloucester Comfort Score for patient comfort was documented. Amongst 69 cases enrolled for TNE evaluation, 97% of cases had an adequate mapping of disease extent, and 100% adequacy of biopsy material. General anaesthesia could be avoided in 92.75% of patients. TNE took a median time of 8 min. Synchronous oesophageal tumours were seen in 5.8% of patients. There were no complications and 74% patients did not experience any discomfort. TNE appears to be simple, safe, efficient office based diagnostic procedure. TNE has the potential to be the new standard of care making DL obsolete.     

Should “atypical follicular cells” in thyroid fine‐needle aspirates be subclassified?

BACKGROUND:

Recently reported Bethesda terminology suggests the use of the term “atypical follicular cells” for thyroid fine‐needle aspirates. Previous work has suggested that some types of “atypical follicular cells” have different risks of malignancy.

METHODS:

The author reviewed the results of all thyroid aspirations with surgical resection performed during the past 13 years at our institution, subclassified the “atypical follicular cells,” and compared their relative risk of malignancy.

RESULTS:

During the 13 years in question, a total of 7089 cases were aspirated with 1331 resections. A total of 548 (14%) of all cases were classified as “atypical follicular cells,” and 204 (37%) were resected with an overall risk of malignancy of 25%. The risk of malignancy for atypical follicular cells subclassified as “rule out papillary carcinoma” was significantly higher (38%) than the other atypical cells. The risk of “rule out Hurthle cell neoplasm” was, at 7%, significantly lower than the other cases of atypical follicular cells (P<.001 and P<.02, respectively).

CONCLUSIONS:

Different types of “atypical follicular cells” have significantly different risks of malignancy. This disparity of risk should be communicated by the cytologist. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.     

Resectable,borderline, and locally advanced pancreatic cancer—“the good,the bad,and the ugly” candidates for surgery?

The possibility of surgical resection strongly overrules medical oncologic treatment and is the only modality, causa sine qua non, long-term survival can be achieved in patients with pancreatic cancer. For this reason, the clinical classification of local resectability, subdividing tumors into resectable, borderline resectable, and locally advanced cancer, that is very technical in nature, is the one most widely used and accepted. As multimodality treatment with potent agents, particularly in the neoadjuvant setting, seems to be stepping forward as the new standard of treatment of pancreatic cancer, the established technical surgical landmarks tend to get challenged. This review aims to highlight the grey zones in the current classifications for local tumor involvement with respect to the observed patient outcome in the current multimodality treatment era. It summarizes the latest reported series on the outcome of resected primary resectable, borderline and locally advanced pancreatic cancer, and particularly vascular resections during pancreatectomy, in the background of different types of neoadjuvant therapy. It also hints what the new horizons of cancer biology tend to reveal whenever the technical hinders start being pushed aside. The current calls for the necessity of re-classification of the clinical categories of pancreatic cancer, from technically oriented to biology-focused individualized approach, are being elucidated.     

Linking Intermediate to Final “Real-World” Outcomes: Is Financial Toxicity a Reliable Predictor of Poorer Outcomes in Cancer?

Traditionally, economic evaluations are based on clinical trials with well-defined patient populations that exclude many patient types. By contrast, studies that incorporate general patient populations end up including those in lower income categories, some of whom have significant financial burdens (often described as financial toxicity) related to their care. Consideration of these patient burdens when examining the incremental cost-effectiveness of newer treatments from a clinical trial perspective can result in differing conclusions regarding cost-effectiveness. The challenge is to reliably assess the link between financial toxicity, quality of life and potential decisions to forego or delay care. It is also well-documented that these financial effects are not evenly distributed across populations, with those with low income and of black or Latino decent being most affected. There is a paucity of literature in this space, but some of the early work has suggested that for lung, breast, colorectal and ovarian cancers there are poorer quality-of-life scores and/or shorter overall survival for those experiencing financial toxicity. Hence, we may see both a lower quality of life and a shorter duration of life for these populations. If this is the case, additional considerations include: are the benefits of newer, more-expensive treatment strategies muted by the lack of adherence to these newer treatments due to financial concerns, and, if true, can these effects be effectively quantified as “real-world” outcomes? This rapid review examines these possibilities and the steps that may be required to examine this reliably.     

Screening for Colorectal Cancer Leading into a New Decade: The “Roaring ‘20s” for Epigenetic Biomarkers?

Colorectal cancer (CRC) has an important bearing (top five) on cancer incidence and mortality in the world. The etiology of sporadic CRC is related to the accumulation of genetic and epigenetic alterations that result in the appearance of cancer hallmarks such as abnormal proliferation, evasion of immune destruction, resistance to apoptosis, replicative immortality, and others, contributing to cancer promotion, invasion, and metastasis. It is estimated that, each year, at least four million people are diagnosed with CRC in the world. Depending on CRC staging at diagnosis, many of these patients die, as CRC is in the top four causes of cancer death in the world. New and improved screening tests for CRC are needed to detect the disease at an early stage and adopt patient management strategies to decrease the death toll. The three pillars of CRC screening are endoscopy, radiological imaging, and molecular assays. Endoscopic procedures comprise traditional colonoscopy, and more recently, capsule-based endoscopy. The main imaging modality remains Computed Tomography (CT) of the colon. Molecular approaches continue to grow in the diversity of biomarkers and the sophistication of the technologies deployed to detect them. What started with simple fecal occult blood tests has expanded to an armamentarium, including mutation detection and identification of aberrant epigenetic signatures known to be oncogenic. Biomarker-based screening methods have critical advantages and are likely to eclipse the classical modalities of imaging and endoscopy in the future. For example, imaging methods are costly and require highly specialized medical personnel. In the case of endoscopy, their invasiveness limits compliance from large swaths of the population, especially those with average CRC risk. Beyond mere discomfort and fear, there are legitimate iatrogenic concerns associated with endoscopy. The risks of perforation and infection make endoscopy best suited for a confirmatory role in cases where there are positive results from other diagnostic tests. Biomarker-based screening methods are largely non-invasive and are growing in scope. Epigenetic biomarkers, in particular, can be detected in feces and blood, are less invasive to the average-risk patient, detect early-stage CRC, and have a demonstrably superior patient follow-up. Given the heterogeneity of CRC as it evolves, optimal screening may require a battery of blood and stool tests, where each can leverage different pathways perturbed during carcinogenesis. What follows is a comprehensive, systematic review of the literature pertaining to the screening and diagnostic protocols used in CRC. Relevant articles were retrieved from the PubMed database using keywords including: “Screening”, “Diagnosis”, and “Biomarkers for CRC”. American and European clinical trials in progress were included as well.     

“Watchful waiting” for metastatic colorectal cancer,antediluvian or an option to be considered again?

Aim: The role of chemotherapy in metastatic colorectal cancer (mCRC) is firmly established and the option of watchful waiting (WW) has become an alternative rarely considered. However, there may be a group of patients who are diagnosed with low volume and asymptomatic disease and who may be suitable for a WW plan. Methods: From the South Australian Cancer Registry for mCRC we examined cancer characteristics and outcomes of patients who were suitable for chemotherapy but had their treatment delayed by more than 3 months from diagnosis of metastatic disease. Results: Data from 417 mCRC patients who received chemotherapy as first intervention have been entered in the Registry to date and 38 (9.1%) had chemotherapy commencement delayed by more than 3 months from diagnosis. Their median age was 76.7 years (range 38–85). Overall 87% of patients had metachronous metastatic cancer with a median time to recurrence of 2.1 years (range 0.53–7.71) and 65.5% had single organ metastasis. Median delay from the diagnosis of metastatic disease to chemotherapy was 5.03 months (range 3–28). The median survival has yet to be reached. The 2‐year overall survival is 65%. Conclusion: We found that almost 10% of all patients with mCRC had a delay in the initiation of chemotherapy, with most due to a WW approach based on case note review. Patients with a delay in chemotherapy initiation are more likely to have a single organ site of metastatic disease and are older than those who do not. Despite the treatment delay, there is no evidence of a negative impact on survival.     

FOLFOXIRI plus Bevacizumab Versus FOLFOX plus Panitumumab for Metastatic Left‐Sided RAS/BRAF Wild‐Type Colorectal Cancer: Which “Side” Are You On?

This commentary focuses on the results of the study by Pietrantonio et al., which evaluated the clinical conundrum of triplet versus doublet chemotherapy in combination with targeted therapy for metastatic left-sided RAS/BRAF wild-type colorectal cancer and appears in this issue. Both FOLFOXIRI [fluorouracil, leucovorin, oxaliplatin, and irinotecan] plus bevacizumab and FOLFOX [fluorouracil, leucovorin, and oxaliplatin] plus panitumumab have shown impressive activity in this population; however, the two have not been directly compared. The article by Pietrantonio et al. presents a propensity score-adjusted analysis using information from five previous randomized trials and provides best available evidence comparing these regimens. This commentary will discuss their results and how their findings fit in current treatment paradigms.     

“What about diet?” A qualitative study of cancer survivors' views on diet and cancer and their sources of information

Given the abundance of misreporting about diet and cancer in the media and online, cancer survivors are at risk of misinformation. The aim of this study was to explore cancer survivors' beliefs about diet quality and cancer, the impact on their behaviour and sources of information. Semi‐structured interviews were conducted with adult cancer survivors in the United Kingdom who had been diagnosed with any cancer in adulthood and were not currently receiving treatment (n = 19). Interviews were analysed using Thematic Analysis. Emergent themes highlighted that participants were aware of diet affecting risk for the development of cancer, but were less clear about its role in recurrence. Nonetheless, their cancer diagnosis appeared to be a prompt for dietary change; predominantly to promote general health. Changes were generally consistent with healthy eating recommendations, although dietary supplements and other non‐evidence‐based actions were mentioned. Participants reported that they had not generally received professional advice about diet and were keen to know more, but were often unsure about information from other sources. The views of our participants suggest cancer survivors would welcome guidance from health professionals. Advice that provides clear recommendations, and which emphasises the benefits of healthy eating for overall well‐being, may be particularly well‐received.     

Does “in situ lymphoma” occur as a distinct step in the development of nodular lymphocyte‐predominant Hodgkin lymphoma?

The concept of in situ neoplasia, already well acknowledged in epithelial tumors, has now been extended to lymphoid neoplasms. Among germinal center (GC)-derived lymphomas, a type of "in situ follicular lymphoma (FL)" has been described in which cells that strongly express BCL2 are observed in histologically abnormal follicles. In this commentary, the author suggests that another GC-derived lymphoma, ie, nodular lymphocyte-predominant Hodgkin lymphoma with a micronodular pattern in which small GCs or broken-up GCs are present within nodules, may be regarded as an early lesion limited to GC. Like "in situ FL," this is likely to be an in situ step that potentially leads to overt lymphoma.