Driving Safely After Cancer Diagnosis

Background

The World Health Organisation emphasises that cancer is among the leading causes of morbidity and mortality worldwide. (1)

Approximately 4 million new patients are diagnosed each year and 8.2 Million cancer related deaths occurred in 2012. (2)

Cancer is the second-leading cause of death in the United States. (3)

It is expected that around 70% of new patients will be diagnosed with cancer over the next 2 decades.

For men, the 5 most common areas where cancer was diagnosed in 2012 were the lung, prostrate, colorectal, stomach and liver cancer.

For ladies the 5 most common sites of cancer diagnosis were the breast, colorectal, lung, cervix and stomach.

What is Cancer?

Cancer is defined as any one of a large number of diseases characterized by the development of abnormal cells that divide uncontrollably and have the capability to intrude and destroy normal body tissue.

 It also often has the ability to spread throughout your body and this process is known as metastases which is often the major cause of death from cancer.

Cancer arises from one single cell.

The transformation from a normal cell into a tumour cell is a multistage process, typically a development from a pre-cancerous lesion to malignant tumours.

These changes are often the result of the interaction between a person's genetic factors and groups of external agents that include:

• physical carcinogens, such as ultraviolet and ionizing radiation;
• chemical carcinogens, such as asbestos, components of tobacco smoke, aflatoxin (a food contaminant) and arsenic (a drinking water contaminant); and
• biological carcinogens, such as infections from certain viruses, bacteria or parasites.

What are the Risk Factors of Cancer?

Approximately 1/3 of cancer are due to the 5 leading behavioural and dietary risk factors that include:

• High Body Mass Index
• Low Fruit and Vegetable Intake
• Lack of Physical Activity
• Tobacco Use
• Alcohol Use

Tobacco use causes around 20% of global cancer deaths and around 70% of global lung cancer deaths.

Cancer may be caused by viral infections such as HBV/HCV and HPV that are responsible for up to 20% of cancer deaths in low- and middle-income countries (4).

Over 60% of world’s total new annual cases occur in Africa, Asia and Central and South America.

These regions account for 70% of the world’s cancer deaths.

It is estimated that annual cancer cases will rise from 14 million in 2012 to 22 within the next 2 decades.

The cancer rises substantially with age, most likely due to a build-up of risks for specific cancers that increase with age

The overall risk accumulation is combined with the tendency for cellular repair mechanisms to be less effective as a person grows older.

How Can the Burden of Cancer be Reduced?

There has been a rapid acceleration in the knowledge about the causes of cancer, and interventions to prevent and manage the disease is extensive.

We can reduce and control cancer by implementing evidence-based strategies for cancer prevention, its early detection of cancer and management of patients with this disease.

There are many cancers that have a high chance of cure if detected early and treated adequately.

Survival rates are improving for many kinds of cancer due to improvements in cancer screening and cancer treatment.

Symptoms

Signs and symptoms caused by cancer may vary depending to what part of the body is affected.

Some general signs and symptoms (3) associated with, but not specific to, cancer, include:

• Fatigue
• Lump or area of thickening that can be felt under the skin
• Weight changes, including unintended loss or gain
• Skin changes, such as yellowing, darkening or redness of the skin, sores that won’t heal, or changes to existing moles
• Changes in bowel or bladder habits
• Persistent cough or trouble breathing
• Difficulty swallowing
• Hoarseness
• Persistent indigestion or discomfort after eating
• Persistent, unexplained muscle or joint pain
• Persistent, unexplained fevers or night sweats
• Unexplained bleeding or bruising

Complications

Cancer and its treatment may cause several complications such as:

• Pain.Pain may be caused by cancer or by its treatment, though not all cancer is painful. Medications and other approaches can effectively treat cancer-related pain.
• Fatigue.Fatigue in people with cancer has many causes, but may often be managed. Fatigue related to chemotherapy or radiation therapy treatments is common, but it's usually temporary.
• Difficulty breathing.Cancer or cancer treatment may cause a feeling of being short of breath. Treatments may bring relief.
• Nausea.Certain cancers and cancer treatments may cause nausea. Your physician may sometimes predict if your treatment is likely to cause nausea. Medications and other therapies may help you prevent or decrease nausea.
• Diarrhoea or constipation.Cancer and cancer treatment may affect your bowels and cause diarrhoea or constipation.
• Weight loss.Cancer and cancer treatment can cause weight loss. Cancer steals food from normal cells and deprives them of nutrients.

This is often not affected by how many calories or what kind of food is eaten; it's difficult to treat.

In most cases, using artificial nutrition through tubes into the stomach or vein does not help change the weight loss.

• Chemical changes in your body.Cancer can upset the normal chemical balance in your body and increase your risk of serious complications.

Signs and symptoms of chemical imbalances might include frequent urination, excessive thirst, constipation and confusion.

• Brain and nervous system problems.Cancer can press on nearby nerves and cause pain and loss of function of one part of your body.

Cancer that involves the brain may cause headaches and stroke-like signs and symptoms, such as weakness on one side of your body.

• Unusual immune system reactions to cancer.In some cases the body's immune system may react to the presence of cancer by attacking healthy cells.

Called paraneoplastic syndrome, these very rare reactions can lead to a variety of signs and symptoms, such as difficulty walking and seizures.

• Cancer that spreads.As cancer advances, it may spread to other parts of the body. Where cancer spreads depends on the type of cancer.
• Cancer that returns.Cancer survivors have a risk of cancer recurrence.

Some cancers are more likely to recur than others.

Ask your physician about what you can do to reduce your risk of cancer recurrence.

Your doctor may devise a follow-up care plan for you after treatment.

This plan may include periodic scans and exams in the months and years after your treatment, to look for cancer recurrence.

Tests and Diagnosis

Diagnosing cancer at its earliest stages frequently provides the best chance for a cure.

Doctors will discuss with their patient what types of cancer screening may be appropriate for them.

For a few cancers, studies show screening tests can save lives by identifying cancer early.

For other cancers, screening tests are suggested only for people with increased risk.

Various medical organizations and patient-advocacy groups have recommendations and guidelines for cancer screening that will be discussed with your doctor.

Cancer Diagnosis

Several approaches to diagnose cancer are usually taken:

• Physical exam.Your physician may feel areas of your body for lumps that may indicate a tumour.

During a physical exam, they may look for abnormalities, such as changes in skin colour or enlargement of an organ that may indicate the presence of cancer.

• Laboratory tests.Laboratory tests like urine and blood tests, may assist your physician identify abnormalities that can be caused by cancer.

For example in people with leukaemia, a complete blood count may reveal an unusual number or type of white blood cells.

• Imaging tests.Imaging tests allow your doctor to study your bones and internal organs in a non-invasive manner.

Imaging tests used in diagnosing cancer may include a computerized tomography (CT) scan, bone scan, magnetic resonance imaging (MRI), positron emission tomography (PET) scan, ultrasound and X-ray, among others.

• Biopsy.During a biopsy, a sample of your cells are taken for testing in the laboratory. There are several ways of collecting a sample.

The appropriate biopsy procedure will be selected that depends on your type of cancer and its location. In most cases, a biopsy is the only way to definitively diagnose cancer.

In the laboratory, physicians examine cell samples under the microscope.

Normal cells look uniform, with similar sizes and orderly organization. However cancer cells look less orderly, with varying sizes and without apparent organization.

Cancer Stages

Once diagnosed, your doctor will work to determine the extent (stage) of your cancer. Your doctor uses your cancer's stage to determine the best treatment options and your chances for a cure.

Staging tests and procedures may include imaging tests, such as bone scans or X-rays, to see if cancer has spread to different areas of the body.

Cancer stages are generally indicated by Roman numerals — I through IV, with higher numerals indicating more advanced cancer.

In some cases, cancer stage is indicated using letters or words.

Treatment and Drugs

Many cancer therapies are available.

Your treatment options will depend on several factors, such as the type and stage of your cancer, your general health, and your preferences.

Together with your physician the benefits and risks of each cancer treatment are discussed to determine which is best for you.

Goals of Cancer Treatment

Cancer treatments have different objectives, such as:

• Cure.The goal of treatment is to achieve a cure for your cancer, allowing you to live a normal life span.

This may or may not be possible, depending on your specific situation.

• Primary treatment.The goal of a primary treatment is to completely eradicate the cancer from your body or kill the cancer cells.

Any cancer treatment can be used as a primary treatment, but the most common primary cancer treatment for the most common cancers is surgery.

If your cancer is particularly sensitive to radiation therapy or chemotherapy, that therapy may serve as your primary treatment.

• Adjuvant treatment.The goal of adjuvant therapy is to kill any cancer cells that may remain after primary treatment in order to reduce the chance that the cancer will recur.

Any cancer treatment can be used as an adjuvant therapy.

Common adjuvant therapies include radiation therapy, chemotherapy, radiation and hormone therapy.

• Palliative treatment.Palliative treatments may help relieve side effects of treatment or signs and symptoms caused by cancer itself.

Surgery, radiation, chemotherapy and hormone therapy can all be used to relieve signs and symptoms.

Medications may relieve symptoms such as pain and shortness of breath.

Palliative treatment may be used in conjunction as other treatments intended to cure your cancer.

Cancer Treatments

Doctors have many options when it comes to treating cancer. Cancer treatment choices include:

• Surgery.The goal of surgery is to eradicate the cancer or as much of the cancer as possible.
• Chemotherapy.Chemotherapy uses drugs to kill cancer cells.
• Radiation therapy.Radiation therapy uses high-powered energy beams, such as X-rays, to kill cancer cells.

Radiation treatment can come from a machine outside your body (external beam radiation), or it may be placed inside your body (brachytherapy).

• Stem cell transplant.Stem cell transplant is also known as bone marrow transplant.

Your bone marrow is the material inside your bones that manufactures blood cells from blood stem cells.

A stem cell transplant can use your own stem cells or stem cells from a donor.

A stem cell transplant allows the physician to use higher doses of chemotherapy to treat your cancer.

It may also be used to replace diseased bone marrow.

• Immunotherapy.Immunotherapy, also known as biological therapy, uses your body's immune system to fight cancer.

Cancer survives unchecked in your body because your immune system doesn't recognize it as an intruder.

Immunotherapy can help your immune system "visualize” the cancer and attack it.

• Hormone therapy.Some types of cancer are fuelled by your body's hormones. Examples include breast cancer and prostate cancer.

Removing those hormones from the body or blocking their effects may cause the cancer cells to stop growing.

• Targeted drug therapy.Targeted drug treatment focuses on specific irregularities within cancer cells that allow them to survive.
• Clinical trials.Clinical trials are studies to investigate new methods of treating cancer.

Other treatments may be available to you, depending on your type of cancer.

Alternative Medicine

Alternative medicine options may help you manage with side effects of cancer and cancer treatment, such as fatigue, nausea and pain.

Your physician may suggest what alternative medicine options may offer some benefit.

They will discuss whether these therapies are safe for you or if they may interfere with your cancer treatment.

10 Alternative Medicine Options That May Be Helpful For People With Cancer

These alternative cancer treatments have shown some promise in helping people with cancer.

• Acupuncture.Acupuncture is not safe if you're taking blood thinners or if you have low blood counts, so check with your doctor first.
• Aromatherapy.Aromatherapy may be helpful in relieving nausea, pain and stress.

 People with cancer that is estrogen sensitive, such as some breast cancers, should avoid applying large amounts of lavender oil and tea tree oil to the skin.

• Exercise.Exercise may help you manage signs and symptoms during and after cancer treatment.

Mild exercise may help relieve fatigue and stress and help you sleep better.

Numerous studies show that an exercise program can help people with cancer live longer and improve their overall quality of life.

Start slowly, adding more exercise as you go.

Aim to work your way up to at least 30 minutes of exercise most days of the week.

• Hypnosis.Hypnosis may be helpful for people with cancer who are experiencing anxiety, pain and stress.

It may also help prevent anticipatory nausea and vomiting that can occur if chemotherapy has made you sick in the past.

When performed by a certified therapist, hypnosis is safe.

However tell your therapist if you have a history of mental illness.

• Massage.Studies have found massage can be helpful in relieving pain in people with cancer.

It may also help relieve anxiety, fatigue and stress.

Massage can be safe if you work with a knowledgeable massage therapist.

Many cancer centers have massage therapists on staff, or your doctor can refer you to a massage therapist who regularly works with people who have cancer.

Don't have a massage if your blood counts are very low.

Ask the massage therapist to avoid massaging near surgical scars, radiation treatment areas or tumours.

If you have cancer in your bones or other bone diseases, such as osteoporosis, ask the massage therapist to use light pressure, rather than deep massage.

• Meditation.Meditation may help people with cancer by relieving anxiety and stress.

Meditation is generally safe.

You can meditate on your own for a few minutes once or twice a day or you can take a class with an instructor.

• Music therapy.Music therapy may help relieve pain and control nausea and vomiting.

Music therapy is safe and doesn't require any musical talent to participate.

Many medical centers have certified music therapists on staff.

• Relaxation techniques.Relaxation techniques are methods of focusing your attention on calming your mind and relaxing your muscles.

They may include activities such as visualization exercises or progressive muscle relaxation.

Relaxation techniques can be helpful in relieving anxiety and fatigue.

They may also help people with cancer sleep better.

Relaxation techniques are safe.

Tai chi. Tai chi is a form of exercise that uses gentle movements and deep breathing.

Practicing tai chi may help relieve stress.

Tai chi is generally safe but it is still essential to talk to your doctor before beginning tai chi. Don't do any tai chi moves that cause pain.

• Yoga.Yoga combines stretching exercises with deep breathing

Yoga may provide some stress relief for people with cancer and it has also been shown to improve sleep and reduce fatigue.

Before beginning a yoga class, ask your doctor to recommend an instructor who regularly works with people with health concerns, such as cancer.

 Yoga that causes pain should be avoided.

You may find some alternative treatments work well together. For instance, deep breathing during a massage may provide further stress relief.

Nutrition and Cancer

Nutrition may play an increasingly important role in the management of cancer as more research unfolds in this area.

Walnut (Juglans regia L.) contains around 20-25 % protein with abundant essential amino acids.

Walnut protein hydrolysates were tested, for the first time, against the viability of human breast (MDA-MB231) and colon (HT-29) cancer cell lines.

MTT, [3-(4, 5dimethylthiazolyl)-2, 5-diphenyl-tetrazolium bromide], assay was used to assess in vitro cancer cell viability upon treatment with the peptide fractions.

The peptide fractions showed in vitro cell growth inhibition of 63 ± 1.73 % for breast cancer and 51 ± 1.45 % for colon cancer cells.(5)

Recent epidemiological studies have confirmed an inverse association between frequent nut consumption and cancer mortality (6-8). 

Association between nut consumption and total and cause-specific mortality has been recently investigated in a study (6) comprising 76464 women from the Nurse’s Health Study (NHS) and 42498 men from the Health Professionals Follow-Up Study (HPFS).

This study revealed a statistically significant inverse correlation between frequent nut consumption and total mortality among women and men.

The inverse association remained mainly unaffected after removal of participants who had never smoked, or with exceptionally high or low body mass index (BMI), or with diabetes at baseline and after other adjustments. 

Further research needs to be done in well controlled clinical trials to evaluate the potential benefits of walnuts for various cancer patients.

Diets high in cruciferous vegetables are associated with lower risk of incidence of prostate cancer, including aggressive forms of this disease.

Numerous worldwide studies show an inverse relationship between consumption of cruciferous vegetables (including members of the Brassicacea family) and the risk of neoplastic diseases has been observed, namely in colorectal, gastric, lung, breast, prostate, bladder, and endometrial cancers (9,10).

Furthermore when 20 patients with recurrent prostate cancer were evaluated with 200 μmoles/day of sulforaphane-rich extracts, there was a significant lengthening of the on-treatment PSA doubling time (PSADT) compared with the pre-treatment PSADT [6.1 months pre-treatment vs. 9.6 months on-treatment (p?=?0.044)] (11)

A review published in 2007 by the American Institute for Cancer Research (AICR) drew attention to the benefits of increased cabbage consumption in pancreatic ductal adenocarcinoma patients. (12)

Kirsh and colleagues observed the significantly decreased risk of extra-prostatic manifestation of prostate cancer (stage III or IV tumours) correlated with an increase in the consumption of cruciferous vegetables, especially broccoli which is rich in sulforaphane and quercetin (P?=?0,02) (13). 

Further pioneering research is progressing with the POUDER trial is the first clinical pilot trial to test the feasibility of an intake of freeze-dried broccoli sprouts as an additive of palliative chemotherapy in surgically non-resectable, advanced pancreatic cancer. (14)

 A Mediterranean diet rich in fruits, vegetables, fish, and olive oil can reduce the risk of cancer by 12%, supporting the conclusion that dietary changes could be highly beneficial in cancer prevention (15,16,)

What About Fitness To Drive After Being Diagnosed With Cancer?

In the UK it is not necessary to tell the Driver and Vehicle Licensing Agency (DVLA) that you have cancer unless (17):

• you develop problems with your brain or nervous system
• your doctor says you might not be fit to drive
• you’re restricted to certain types of vehicles or vehicles that have been adapted for you
• your medication causes side effects which could affect your driving

In Australia, new guidelines came into effect on the 1 October 2016 to determine a person’s fitness to drive.

These guidelines were determined by working closely with health professionals, driver licensing authorities and consumer groups.

The latest updates provide clearer guidance for health professionals to support consistent assessment and decision making. (18)

Does Frequent Driving Increase Risk of Cancer?

The relationship between employment and cancer of the lower urinary tract in Detroit was examined by means of a population-based case-control study conducted as part of the National Bladder Cancer Study.

303 white male patients with transitional or squamous cell carcinoma of the lower urinary tract and 296 white male controls selected from the general population of the study area were interviewed to obtain lifetime occupational histories.

 D.T Silverman and colleagues found that truck drivers have a significant increased risk of lower urinary tract cancer [relative risk = 2.1; 95% confidence interval (Cl) = 1.4-4.4]. (19)

Interestingly a significant trend in risk was shown with increasing duration of employment as a truck driver (P = 0.004); the relative risk estimated for truck drivers employed at least 10 years was 5.5 (Cl = 1.8-17.3).

Furthermore, truck drivers with a history of operating vehicles with diesel engines experienced a significant elevated risk compared to non-truck drivers (relative risk = 11.9; Cl = 2.3-61.1), but it was not possible to evaluate if the increased risk observed among truck drivers was attributable to diesel exposure.

Does Cancer Impair Driving Motor Vehicles?

Continuous reaction times (CRTs) and subjective assessment of pain intensity (PVAS) and sedation (SVAS) were compared in 14 cancer patients during chronic oral opioid therapy (daily doses of morphine: 130-400 mg) and subsequent stable epidural opioid therapy (daily doses of morphine: 32-240 mg). (20)

Twenty healthy subjects had their CRT’s measured as controls.

CRT results were summarized using 10%, 50% and 90% percentiles.

On the basis of these values a 'variation index' was calculated (90-10%): 50%, describing the spread of the reaction time values.

Calculation of confidence limits of median differences showed absolutely no tendency towards differences in CRT between the treatments.

Only four patients experienced both increased pain relief and less sedation on epidural opioids.

Comparing CRT percentiles of the cancer patients with the controls, differences were found between the control group and the oral opioid group, the latter being statistically significantly slower in the 90% percentiles (P = 0.018) and variation indexes (P = 0.018).

There were no statistically significant differences found in PVAS, SVAS and CRT before and after initiation of epidural opioid administration.

The authors concluded that at this dose level of chronic opioid treatment, the advantage of epidural administration seems doubtful.

A Banning and Colleagues examined Continuous Reaction Time (CRT) in cancer patients receiving peripherally acting analgesics either alone (n = 16) or in combination with opioids (n = 16). (21)

Comparison was performed matching the patients from each group for age and performance status.

Statistically significant prolongations of CRT and higher sedation scores were seen in the opioid group, while performance status did not have any influence on CRT.

Anneli Vainio and co-investigators examined the effects of continuous morphine medication, psychological and neurological tests in two groups of cancer patients who were similar apart from experience of pain. (22)

24 were on continuous morphine (mean 209 mg oral morphine daily) for cancer pain; and 25 were pain-free without regular analgesics..

These authors found that although the results were a little worse in the patients taking morphine, there were no significant differences between the groups in intelligence, vigilance, concentration, fluency of motor reactions, or division of attention.

Of the neural function tests, reaction times (auditory, visual, associative), thermal discrimination, and body sway with eyes open were similar in the two groups; only balancing ability with closed eyes was worse in the morphine group.

These findings indicate that, for cancer patients receiving long-term morphine treatment with stable doses, there were only a slight and selective effect on functions related to driving.

Guidelines to Improve Driver Safety

It is important to provide practical advice for patients to enable them to drive motor vehicles safely. Some very helpful strategies may include (23, 24):

• Driving is a personal decision which needs to be reviewed constantly and they should not drive if they feel sedated.
• Stable doses of opioids and no concomitant use of other psychoactive drugs
• The doctor, and only one prescriber, should have continuous control of the therapy.

The patients should not make changes to their medication regimens separately.

• Written documentation of the advice should be provided.
• Despite the above information, the doctor should not be able to recommend if a patient can drive.

The research information available should be quoted and opioid side effects mentioned.

• The precise question of whether a patient can drive may only be determined in a driving simulator and/or on-road driving tests.

Conclusion

Currently around 8.2 million people die from cancer and 1.2 million die from road traffic accidents each year.

If all the strategies that are outlined above are implemented worldwide, this will greatly reduce the cancer death rate.

However we still need to continually strive to find more minimally sedating drugs in every therapeutic area to reduce the death rate from motor vehicle accidents.

References

1)   World Health Organisation Fact Sheet Number 297 Updated February 2015.https://www.who.int/mediacentre/factsheets/fs297/en/

2)   World Cancer Report 2014. https://publications.iarc.fr/Non-Series-Publications/World-Cancer-Reports/World-Cancer-Report-2014

3)   Cancer. Definition Mayo Foundation for Medical Education and Research. 1998-2016.https://www.mayoclinic.org/diseases-conditions/cancer/basics/definition/con-20032378

4)   de Martel C, Ferlay J, Franceschi S, et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. The Lancet Oncology 2012;13: 607-615

5)   Jahanbani R, Ghaffari SM, Salami M, Vahdati K, Sepehri H, Sarvestani NN, Sheibani N, Moosavi-Movahedi AA. Antioxidant and Anticancer Activities of Walnut (Juglans regia L.) Protein Hydrolysates Using Different Proteases. Plant Foods Hum Nutr. 2016 Sep 27. [Epub ahead of print]

6)   Bao Y, Han J, Hu FB, et al. Association of nut consumption with total and cause-specific mortality. N Engl J Med. 2013; 369(21):2001–2011.

7)   Guasch-Ferré M, Bulló M, Martínez-González Má, et al. Frequency of nut consumption and mortality risk in the PREDIMED nutrition intervention trial. BMC Med. 2013; 11:164.

8)   Bao Y, Hu FB, Giovannucci EL, et al. Nut consumption and risk of pancreatic cancer in women. Br J Cancer. 2013; 109(11):2911–2916.

9)   Herr I, Lozanovski V, Houben P, Schemmer P, Büchler MW: Sulforaphane and related mustard oils in focus of cancer prevention and therapy. Wien Med Wochenschr. 2013, 163: 80-88. 10.1007/s10354-012-0163-3.

10) Fahey JW, Zhang Y, Talalay P: Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc Natl Acad Sci USA. 1997, 94: 10367-10372. 10.1073/pnas.94.19.10367.

11) Alumkal JJ, Slottke R, Schwartzman J, Cherala G, Munar M, Graff JN, Beer TM, Ryan CW, Koop DR, Gibbs A Gao L, Flamiatos JF, Tucker E, Kleinschmidt R, Mori M. A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer. Invest New Drugs. 2015 Apr; 33(2):480-9. doi: 10.1007/s10637-014-0189-z. Epub 2014 Nov 29.

12) Forman D, Burley V, Cade J, Greenwood D, Moreton J, Chan D, Tu Y-K, Gordon I, Thomas J, McColl K: The associations between food, nutrition and physical activity and the risk of pancreatic cancer and underlying mechanisms. World Cancer Research Fund. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. 2007, Washington, DC: AICR

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14) Vladimir J Lozanovski, Philipp Houben, Ulf Hinz Thilo Hackert, Ingrid Herr Peter Schemmer.Pilot study evaluating broccoli sprouts in advanced pancreatic cancer (POUDER trial) - study protocol for a randomized controlled trial.Trials.2014.15:204.DOI:10.1186/1745-6215-15-204

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16) La Vecchia C Association between Mediterranean dietary patterns and cancer risk .Nutr Rev. 2009; 67(1):S126–S129.

17) GOV.UK. Cancer and Driving.23 September 2016 https://www.gov.uk/cancer-and-driving 

18) Austroads. Assessing Fitness to Drive.https://www.austroads.com.au/drivers-vehicles/assessing-fitness-to-drive

19) Silverman DT, Hoover RN, Albert S, Graff KM. Occupation and cancer of the lower urinary tract in Detroit. J Natl Cancer Inst. 1983 Feb; 70(2):237-45.

20) Sj?gren P, Banning A. Pain, sedation and reaction time during long-term treatment of cancer patients with oral and epidural opioids. Pain. 1989 Oct; 39(1):5-11.

21) Banning A, Sj?gren P, Kaiser F. Reaction time in cancer patients receiving peripherally acting analgesics alone or in combination with opioids. Acta Anaesthesiol Scand. 1992 Jul; 36(5):480-2.

22) Anneli Vainio, Juhani Ollila, Esko Matikainen, Peer Rosenberg, Eija Kalso. Driving ability in cancer patients receiving long-term morphine analgesia. Lancet 1995, 346:667-70

23) Fishbain DA, Cutler RB, Rosomoff HL et al. Are opioid-dependent/tolerant patients impaired in driving related skills? A structured evidence-based review. J Pain Symptom Manage 2003; 25:559-77.

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