Approximately 700 Irish people are diagnosed with non-Hodgkin lymphoma (NHL) each year.¹ Furthermore, the number of new cases is increasing by about 3-5% annually,² and it is estimated that it will be as common as breast or lung cancer by 2025.³ This increase can be partly attributed to our ageing population, with 66 being the median age of diagnosis in Ireland.¹ However, in recent years, NHL mortality rates have begun to stabilise. This suggests that the prognosis for NHL patients in Ireland has improved, which is reflected in the increased survival rates. According to recent figures from the National Cancer Registry of Ireland, five-year relative survival has increased from 47.3% in 1994 to 64.1% in 2012.¹ As a result, there are now more NHL survivors in Ireland than ever before.

NHL survivors

The National Cancer Institute considers a person to be a cancer survivor “from the time of diagnosis until the end of life”. Although the growing number of survivors is a welcome sign of progress, this trend also presents a challenge because many of these individuals require significant, ongoing care, such as surveillance for cancer recurrence, screening for new cancers, and care for the long-term effects of their initial treatment. As a result, survivorship should now be seen as a new diagnosis, as well as a new medical speciality in its own right.

Six-in-10 patients who either present with, or transform from an indolent to an aggressive form of NHL (eg. follicular lymphoma → diffuse large B cell lymphoma) can be cured with intense protocols, such as multi-agent chemotherapy as well as additional radiotherapy and, potentially, bone marrow/stem cell transplantation. These aggressive forms tend to have a short natural history, with the greatest risk of relapse being within two years of ending treatment.⁴ However, survivors can be left with long-lasting side-effects such as cardiac dysfunction, cognitive impairment, secondary comorbidities and sexual dysfunction, as well as psychosocial sequelae.

Furthermore, it has been reported that cancer survivors are almost twice as likely to have at least one functional limitation.⁵ These late effects may adversely impact survivors’ health-related quality of life (HRQoL), a multidimensional concept including domains relating to patient physical, mental, emotional and social functioning which has become synonymous with cancer survivorship in recent times.

Multi-level impact

The impact of a NHL diagnosis on the physical health of the survivor is reported on in various forms of literature. A study by Smith et al,⁶ found that those with active NHL disease had poorer physical functioning and QoL than disease-free survivors. Mols et al⁷ found that NHL survivors exhibited significantly lower scores than the normal population for general health perception (GHP)
(P < .001) and vitality (P < .001). 

Furthermore, the psychological impact of diagnosis can result in negative health outcomes for the survivor. Most NHL survivors have undergone chemotherapy, radiotherapy, or a combination of both as part of their treatment. Survivors who have received chemotherapy or who currently had active disease described significantly poorer psychological and social wellbeing and QoL than those who had not.⁸

This can also be seen in a cross sectional exploratory study conducted by Smith et al in 2011⁹ in which it was found that one of the strongest QoL relationships (P < .001) was for post-traumatic stress disorder-like symptoms found in survivors, which were as a result of their diagnosis. It is therefore very clear to see the detrimental impact a cancer diagnosis can have on an individual’s psychological wellbeing and their ability to cope during such an uncertain and stressful time. As well as this, the obvious financial burden associated NHL has been widely reported in many studies,^7,10 in which it has been found that those survivors earning less than a certain income bracket have a poorer QoL outcome.

The Functional Assessment of Cancer Therapy – General (FACT-G) is a standardised, validated, HRQoL measure. It has been used across the literature to demonstrate the effect of having one or more comorbidity coupled with NHL. One such study,¹¹ found that for every point increase in comorbidity score, the FACT-G score was 1.35 points lower. A study conducted by Smith et al in 2009⁶ found that 60% of NHL survivors were either unemployed or retired due to issues related to their condition.

Furthermore, Mols et al⁷ reported that 41% of survivors indicated that they had changed jobs, reduced working hours or stopped working entirely as a result of their cancer.  Other related studies have also found that NHL survivors who were employed reported a higher QoL than those who didn’t, which demonstrates the added benefit of employment to functional wellbeing.^9,11 Functional change at any point in the survivorship trajectory may require changes to housing arrangements as well as the amount of support provided. This QoL domain has gained more attention as the population continues to age in order to accommodate these associated effects on daily living.

QoL research in Ireland

As the number of NHL survivors in Ireland increases, there is a growing need for research focused on quality of life (QoL) outcomes in this population. Our research set about assessing the QoL in an Irish population of non-Hodgkin lymphoma (NHL) survivors. High-grade NHL survivors treated in two university hospitals participated in this cross-sectional study by completing the validated Lymphoma-specific Functional Assessment of Cancer Therapy (FACT-Lym) questionnaire, and the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy Lymphoma Symptom Index-18 (FLymSI-18). The FACT-Lym is centred around the aforementioned generic core questionnaire, the FACT-G. This is a compilation of general questions divided into the four primary QoL domains: physical, social, emotional, and functional well-being. It is considered appropriate for use with patients with any form of cancer, and has also been used and validated in the general population. Our population scored a mean of 94 out of a range of 58-108, with a SD of 13. With regards to lymphoma-specific QoL, this population scored a mean of 60 out of a range of 33-72, with an SD of 10.4 (see Table 1).

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Scales were measured using a score from 1 (not at all) to 4 (very much). Raw data was transformed to linear scores, with high scores indicating a higher level of functioning. Linear regression analysis was used to compare scores according to time since diagnosis. Of 87 questionnaires administered, 47 were completed and returned by NHL survivors (54% response rate).

We found that QoL scores improved from time of diagnosis, with the exception of 4-5 years where scores decreased, before again improving in the following years. After adjusting for age and sex, statistically significant differences were identified 5+ years after diagnosis in emotional, functional wellbeing and global FACT-Lym scores when compared to 1-2 years after diagnosis. Interestingly, our small, mostly private patient population reported higher QoL than larger government-insured American groups.⁶ However, these patients reported ongoing symptoms, long after treatment ended (see Figure 1).

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Discussion

We concluded that QoL improves post diagnosis with a transient decrease at year 4-5 which may represent anxiety prior to being declared ‘cured’ or being discharged from follow-up. The lapse in QoL scores in the 4-5-year category could be related due to the fact that most patients are discharged from long-term care after five years of remaining relapse free. This is also the threshold used in the literature as the definition of ‘long-term’ survivorship. There may be increased anxiety around this time, as found in a study conducted by Thomas et al¹² in which it was found that despite the provision of continued support and guaranteed fast-access return to the clinic if necessary, 28% of patients refused to be discharged, citing that fear of recurrence would be undetected as the most frequent reason.

Furthermore, there may be grounds for this anxiety, as found by Chait et al¹³ that primary care services may find it difficult to cope adequately with the special requirements involved in cancer patient care following discharge, addressing the need to address the further training requirements of GPs in the routine follow-up of cancer patients.

Taking these results into account, a similar study to this conducted by Smith et al6 found that no significant differences were found between short- and long-term NHL survivors on any of the health or QoL measures, suggesting that simply “time out from diagnosis and treatment is not an explanation for such status as cancer, and that psychosocial effects resolve by or continue beyond the conventional five-year threshold”.

Given this finding, this would imply that screening for QoL-related issues related to having been diagnosed with cancer should not conclude prior to the five years post-diagnosis milestone for those who evidenced poor QoL earlier. Other critical elements, such as social support or the alleviation of physical symptoms, play a key role in achieving enhanced functioning, regardless of when these elements occur.

Recommendations

A crucial recommendation going forward is the development of an Irish intervention programme for those who have survived NHL. Extensive international literature exists that demonstrate the benefits of such programmes, including improved functional QoL, decreased health worry, as well as a direct increase in QoL with increased physical activity.^14,15 Such programmes could include strategies such as those outlined by Glynne-Jones et al,¹⁶ who examined the installation of a formal planned system of discharge from the oncology clinic of a district general hospital for long-term cancer survivors. 

The mainstay of this system lay in a written contract between the doctor and the patient, which accepted continuing responsibility after discharge. At four months post discharge, patients were visited in their homes and their views sought on the effectiveness of the contract in terms of reassurance and their experience of being discharged after so many years of follow-up care. By 13 months, only six patients had returned to the clinic, citing anxiety and fear of reoccurrence as the major factors for doing so. The remaining 35 patients appeared to be successfully rehabilitated to primary care.

Our research results were presented by Dr Rebecca Holland at the inaugural American Society of Clinical Oncology (ASCO) Cancer Survivorship Symposium, held in San Francisco in January of this year. This was a unique collaboration between the American Academy of Family Physicians, the American College of Physicians and ASCO. The meeting provided information about survivorship issues that both primary care physicians and oncologists are faced with throughout the cancer care continuum. This included health promotion, long-term side effects, secondary cancer treatment and prevention and, in particular, the survivorship care plan as an invaluable method of patient guidance and reassurance.

There is clearly a lot of ground to cover even still with regards to survivorship care, as presented in a pilot study carried out by Hahn et al, who found that, despite existing evidence based guidelines on post-treatment care, fewer than half of young adults with Hodgkin lymphoma receive all of the recommended services within the first year after treatment.¹⁷ Emphasis was placed on the various modes of cancer survivorship care delivery. This encompassed disease/treatment specific clinics, as well as consultative services in which a one time (+/- annual) consult covers general survivorship issues and distributes the survivorship care plan.

Furthermore, the proposed ‘integrated care’ model sees the survivorship visit embedded within the oncology clinic visit, which in turn proposes to ease the transition into survivorship for the patient.

Conclusion

Going forward, it is hoped that both short- and long-term data collection will further establish QoL as well as functional well-being and symptomatology of NHL survivors in Ireland, with a view to developing and implementing support systems in order to aid the journey through this challenging survivorship trajectory. It is very clear that, in contrary to what was previously believed, it is once the PET scans run cold that the journey of the NHL survivor begins.

Acknowledgements: Dr Brian Bird, consultant oncologist, BSH; Prof Mary Cahill, consultant haematologist, Cork University Hospital (CUH); Dr Deirdre O’ Mahony, consultant oncologist, CUH; Prof Seamus O’Reilly, consultant oncologist, CUH; and Dr Conleth Murphy, consultant oncologist, BSH

References

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2. Lymphoma Forum of Ireland. Guidelines on Diagnosis and Treatment of Malignant Lymphomas (Internet). Ireland: Lymphoma Forum of Ireland; 2010. Available from: http://www.haematologyireland.ie/wp-content/uploads/2016/03/Lymphoma-GuidelinesonDiagnosisandTreatmentofMalignantLymphomas.pdf (Accessed 1/6/16)
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