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Holding hands by the beach

Guest post: Oncological endpoints and human relationships

By Deep Chakrabarti, MD, Senior Resident, Department of Radiotherapy, King George’s Medical University, Lucknow, India


I reach the radiotherapy outpatient department on a Monday morning geared up and ready for the week ahead. With thoughts of a busy day and a busy week lying ahead of me, little do I appreciate then that my experiences over the week will continually repeat in cycles, much like the entire human existence and offer me reflections on life. The pandemic has made many of us re-evaluate ourselves and our relationships, many of which have been strained.

I believe that oncology endpoints can be assumed to mimic human relationships. A 70-year-old frail gentleman has a metastatic oral cavity cancer and is planned for palliative therapy with oral methotrexate. While his overall survival will most likely be a few months, we offer him oral metronomic chemotherapy and supportive care aiming for a decent quality of life. Most chemotherapeutic agents offer a similar overall survival of around six to nine months in the context of advanced or metastatic head and neck cancers. Similarly, in life, some relationships come with an expiry date, no matter what.

A 50-year-old gentleman presents with a recurrence of his locally advanced rectal cancer nine months after completing adjuvant treatment. Our surgical colleagues have seen him, and his disease has been deemed unresectable. He has been started on chemotherapy with oxaliplatin and capecitabine and has tolerated the first two cycles.  I know well it is a matter of time that the drugs will delay progression. Progression-free survival (PFS) is a popular endpoint in oncology research that loosely means the time it takes for a disease to get worse.1 Interpersonal relationships are often subject to intense emotional and mental stress, that require continual repairing. However, situations arise when it may not be possible to start on a clean slate entirely, and one is left with no choice but to accept whatever has happened and move on. In other words, one has to take the inevitable that the relationship cannot be “cured”, but further worsening can be avoided. For some tumours like advanced ovarian or colorectal cancers, PFS may even be a loose surrogate for overall survival and may often be nearly equal to overall survival. Likewise, some relationships may not worsen again after one episode when both parties make conscious efforts to put things behind them and move on.

On Tuesday, I see a 40-year-old lady with visceral dissemination of hormone receptor-positive breast cancer receiving systemic chemotherapy. While she and her family have been counselled about their predicament, they may still have some time with their loved one to fulfil their wishes. Like the overall tenure of each human relationship, overall survival parameters vary grossly from one cancer to another. For example, a metastatic gall bladder cancer is likely to be fatal in a matter of mere months, even with the best available chemotherapy. On the contrary, a man with metastatic prostate cancer can be expected to survive a few years with the current standards of care. 

Overall survival is the gold standard when it comes to measuring the worth of any cancer-directed intervention.2However, in patients or in relationships where one knows that the writing is on the wall, quality of life, or quality of the time left in the relationship is a premium. Quality of life is a crucial metric that seeks to quantify the actual well-being of an individual.3 While one may explore multiple therapeutic options to prolong life, one has to make a conscious decision as to how the prolongation will impact on its quality. Merely prolonging life while impairing its quality is detrimental. Similarly, when one knows that a relationship is irreparable, it is best to consider its quality than to keep trying to prolong it endlessly.

On Wednesday, I get an urgent consultation request for a lady with non-small cell lung cancer admitted in the neurosurgical ward who has presented with acute onset lower limb weakness with bladder and bowel involvement and has been diagnosed to have metastatic spinal cord compression. She is 70 years old with a WHO performance score of 2. The surgeons have already determined she is not a candidate for decompression. She is taken for urgent palliation with a single fraction of radiotherapy, with adequate steroid cover. Similar to the previous example, while her fate is probably already decided, but the urgent intervention offers to improve her quality of life, even if minimally.

On Friday, I get a call for radiotherapy planning for a patient who has cervical cancer with brain metastases and had received primary chemoradiotherapy three years ago. She is 74 years old, with a WHO performance score of 3 and requires continuous oxygen support. A decision is taken not to treat her with radiotherapy to the brain but offer her supportive care. Her three-year disease-free interval reminds me that a repaired relationship may suffer a relapse at any time. And sometimes a relapse can be so devastating that it does not offer much in terms of salvage.

On Saturdays, I see my radiotherapy patients on their weekly follow-up. We have a preponderance of head and neck cancer patients who will often present with grade II or III acute skin and mucosal toxicities as they move into the last weeks of therapy. Acute radiation reactions are defined as those occurring within 90 days of treatment and usually heal entirely with adequate care. However, late reactions or those occurring beyond 90 days persist and never completely heal. Some acute reactions may persist as late reactions, the so-called “consequential late reactions” (for example, chronic xerostomia is a consequential late reaction to acute xerostomia). For human relations, an acute bad episode may be amenable to rationalization and understanding, that may completely disappear like the resolution of acute radiation mucositis. But they may even persist, and then never go away completely. Therefore, the role of supportive care cannot be overemphasized, both in cancer care and in human relations.

The previous year has been a revelation for all of us. While it has subjected us to intense mental, emotional, and physical stress4, we have gained a thorough idea of what is vital in our lives. It is imperative that human relationships are valued on par with professional commitments, and the ongoing global crisis should teach us to prioritize personal contentment over professional gains. A morbidity audit from the CDC in August 2020 depicted that nearly one in four healthcare professionals had considered suicide in the immediately preceding one month for their troubles.5 While this is an alarmingly high number, it depicts the frailties ingrained in each of us and reiterates that before clinicians, we are humans. Even when our human forms are damaged and broken, sometimes beyond repair, empathy and patience for ourselves and our fellow beings might hold the key in this perennial struggle. May the progression-free survival of our relationships always closely mimic their overall survival.6 After all, as said by Rabindranath Tagore, “faith is the bird that feels the light and sings when the dawn is still dark.”

Conflicts of interest: There are no conflicts of interest to declare.

Funding: There is no funding to declare.

References

1         Korn RL, Crowley JJ. Overview: Progression-Free Survival as an Endpoint in Clinical Trials with Solid Tumors. Clin Cancer Res 2013; 19: 2607–12.

2         Driscoll JJ, Rixe O. Overall Survival: Still the Gold Standard. Cancer J 2009; 15: 401–5.

3         Selby P. The value of quality of life scores in clinical cancer research. Eur J Cancer 1993; 29A: 1656–7.

4.        Vallée M, Kutchukian  S , Pradère  B et al. Prospective and observational study of COVID-19’s impact on mental health and training of young surgeons in France. Br J Surg. 2020 Oct;107(11):e486-e488.  doi: 10.1002/bjs.11947.

5         Czeisler MÉ, Lane RI, Petrosky E, et al. Mental Health, Substance Use, and Suicidal Ideation During the COVID-19 Pandemic — United States, June 24–30, 2020. MMWR Morb Mortal Wkly Rep 2020; 69: 1049–57.

6         Lebwohl D, Kay A, Berg W, Baladi JF, Zheng J. Progression-Free Survival. Cancer J 2009; 15: 386–94.

Prioritising Surgical Treatment in Coronavirus Pandemic “Salford Score”

Prof Gordon Carlson CBE FRCS

Background

In light of the need to assess priorities of surgical treatment in a resource-limited environment, NHS England have set out clinical priorities for cancer surgery. However, these priorities do not take into account the vulnerability of the patient to excess morbidity and mortality in the event of Covid-19 infection. It seems evident that, particularly when undertaking elective surgery, the vulnerability of a patient to Covid-19 related morbidity and mortality might be equally important to considerations of the timing of surgery as the underlying disease for which surgery is proposed.

The resource allocation system currently in use at Salford Royal NHS Foundation Trust (which has since been adopted throughout other hospitals at Northern care Alliance) takes both of these factors into account, by producing a score based upon the need to prioritise treatment on purely disease related grounds and also the vulnerability of the patient to Covid-19. The aim is to generate a score which can be used to determine the overall surgical treatment priority of a group of patients, possibly from different surgical subspecialties, when surgical resources have become limited as a result of the Covid-19 pandemic. The score allows different groups of surgeons and hospital management to objectively determine how temporarily limited resources might be allocated. It is meant to help guide collective discussions, not to be a rigid indicator of those patients for whom surgical treatment should be deferred, and it should be used to support, not to replace MDT discussions.

Cancer Surgery Priority

The NHS England Suggested Priority for Cancer surgery is summarised in table 1 below.

PriorityDescription
Priority level 1a• Emergency: operation needed within 24 hours to save life
Priority level 1b• Urgent:operation needed with 72 hours
Based on: urgent/emergency surgery for life threatening conditions such as obstruction, bleeding and regional and/or localised infection permanent injury/clinical harm from progression of conditions such as spinal cord compression
Priority level 2Elective surgery with the expectation of cure, prioritised according to:
• Surgery within 4 weeks to save life/progression of disease beyond operability.
Based on:urgency of symptoms, complications such as local compressive symptoms, biological priority (expected growth rate) of individual cancers

NB. Local complications may be temporarily controlled, for example with stents if surgery is deferred and /or interventional radiology.
Priority level 3Elective surgery can be delayed for 10-12weeks with no predicted negative outcome.
Table 1: NHS England Suggested Priority for Cancer surgery

However we could make resource allocation easier if we devised a simple, objective and consistent way of summarising the two variables which influence decision making – clinical treatment priority and risk of COVID-related adverse outcome, into one numerical score;

The “Salford Score” simplifies this to:

  • Priority 1a = score (P)1
  • Priority 1b = score (P)2
  • Priority 2 = score (P)3
  • Priority 3 = score (P)4

Vulnerability

A second component of this relates to vulnerability of the patient in case of a COVID infection (see table 2).

Vulnerability scoreOutcome in case of COVID infection
Vulnerability level 1• Unlikely to have excess mortality (compared to a completely fit individual < 70 years old) in the event of Covid infection
Vulnerability level 2• Likely to have significant excess mortality compared to a completely fit individual < 70 years old in the event of Covid-19 infection, but would ordinarily receive invasive ventilation in that eventuality
Vulnerability level 3• Extremely likely to succumb to Covid-19 infection and would not ordinarily receive invasive ventilation in that eventuality
Table 2: Vulnerability score

Salford Score

A resource allocation score of PxV, is then calculated so that a fit patient at high risk of imminent death of underlying disease (P1or 2) and unlikely to have excess Covid mortality (V1) would score 1 or 2 (and get urgent surgical treatment), whereas a patient with a non-immediately life threatening condition (P4) for which surgical treatment could be safely be delayed for 12 weeks and who would not, as a result of severe pre-existing medical comorbidity, be intubated etc. should they develop Covid and respiratory failure (V3) would score 12 and we would not proceed to offer surgery until the current resource position changes.