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Chemoradiation Therapy - Concurrent Chemoradiotherapy
Radiation Oncology

Chemoradiation Therapy - Concurrent Chemoradiotherapy

About This Department

 
Medical and Radiation Oncology

For several cancers, chemotherapy given during radiotherapy cures more patients than radiotherapy alone. In head and neck cancer the gain is 6.5 more survivors in every 100.

That figure, measured at five years, comes from a pooled analysis of 50 randomized trials, and comparable gains have been shown in cancers of the cervix, lung, bladder and brain. Every one of those trials also found the combination harder to get through. Expect a six or seven week commitment, with two departments working to one calendar. Send us your pathology report, staging scans and recent blood tests, and our oncologists will tell you whether the combination is advised for you and what the weeks would involve.

6.5 in 100
More head and neck patients alive at five years
6 in 100
More women with cervical cancer alive at five years
26.5% vs 10.4%
Two-year survival in glioblastoma, with and without temozolomide
Free
Joint review by both oncology teams
Free consultation
Chemoradiation, also called concurrent chemoradiotherapy, means that chemotherapy is given during the same weeks as a course of radiotherapy, so that each makes the other more effective against the tumor.

Why give chemotherapy and radiotherapy at the same time?

Oncologists have three ways of ordering the two treatments. Chemotherapy can come first (induction), it can come afterward (adjuvant), or it can run alongside, which is concurrent, and for a group of cancers the concurrent order has beaten the others in direct comparison. The head and neck meta-analysis found a larger benefit from concurrent than from induction chemotherapy. The lung cancer meta-analysis compared concurrent with sequential treatment in the same drugs and doses and found that timing alone changed survival.

Three things the chemotherapy does

It sensitizes the tumor
Drugs such as cisplatin, fluorouracil and temozolomide interfere with the repair of radiation damage in cancer cells. Each day's radiotherapy therefore kills more than it would alone, at drug doses lower than those of chemotherapy given by itself.
It reaches what the beam does not
Radiotherapy treats what is inside the target. Chemotherapy travels in the blood and can act on cancer cells that have already left the area.
It can save the organ
In cancers of the larynx, bladder, anus, cervix and esophagus, chemoradiation is offered as an alternative to removing the organ, with surgery held in reserve for tumors that do not clear.

Which cancers is it used for, and what did the trials find?

Five cancers have the clearest randomized evidence, and each accordion below gives the trial and its numbers.

Head and neck cancer
The MACH-NC meta-analysis pooled individual data from 87 trials and 16,485 patients. Across the 50 trials of concurrent chemotherapy, the risk of death fell by 19 percent and five-year survival rose by 6.5 percentage points. The benefit shrank with age, and the authors found it smaller in older patients. Cisplatin is the standard drug.
Cervical cancer
A meta-analysis of individual data from 18 trials, published in the Journal of Clinical Oncology in 2008, found a 6 percentage point improvement in five-year survival when chemotherapy was added to the same radiotherapy. Local and distant recurrences both fell. Blood count and bowel side effects during treatment rose. Weekly cisplatin is the usual regimen, and internal radiotherapy completes the course.
Lung cancer, stage III
Six trials and 1,205 patients compared concurrent with sequential treatment. Three-year survival was 23.8 percent with concurrent and 18.1 percent with sequential treatment, and the gain at five years was 4.5 points, mainly because the disease in the chest was better controlled.
Glioblastoma
The trial that set the current standard randomized 573 patients at 85 centers to radiotherapy alone or radiotherapy with a daily temozolomide capsule, followed by six monthly cycles of the drug. Median survival was 14.6 against 12.1 months, and two-year survival 26.5 against 10.4 percent. Severe blood count effects occurred in 7 percent.
Bladder cancer, as an alternative to removal
BC2001 randomized 360 patients to radiotherapy with or without fluorouracil and mitomycin. Two years later, 67 percent of the chemoradiation group and 54 percent of the radiotherapy group were alive without disease in the pelvis. Five-year survival was 48 against 35 percent, a difference that did not reach statistical significance.
  • Rectal cancer. Capecitabine tablets with five weeks of radiotherapy before surgery, to shrink the tumor and lower the chance of it returning in the pelvis.
  • Anal cancer. Fluorouracil or capecitabine with mitomycin. Chemoradiation is the primary treatment, and most patients keep normal bowel control and avoid a permanent stoma.
  • Esophageal cancer. Weekly carboplatin and paclitaxel with radiotherapy, before surgery or as definitive treatment.
  • Nasopharynx, larynx preservation, pancreas, stomach after surgery, vulva. Chemoradiation is standard in defined situations for each of these, and the tumor board will explain whether yours is one of them.

What it costs the patient

Read the survival figures again. Most of them amount to four to seven extra survivors in every hundred, a real gain, bought at a price that every patient should hear before agreeing. None of it is trivial. Radiotherapy reactions arrive earlier and run deeper when chemotherapy is on board. For the throat that means a mouth and gullet too sore for solid food, thick saliva, weight loss, and for many patients some weeks on a feeding tube, for the chest it means painful swallowing, and for the pelvis diarrhea, cystitis and sore skin in the groin. On top of those come the effects of the drug itself, which for cisplatin are nausea, kidney strain, ringing in the ears and hearing loss, and for every regimen a fall in blood counts that opens the door to infection.

Severe inflammation of the gullet occurred in 18 percent of lung cancer patients given concurrent treatment and 4 percent given the same treatments one after the other.
Meta-analysis in the Journal of Clinical Oncology, 2010

Nobody should be talked into this treatment. Nobody should be talked out of it by fear alone, either.

Who is fit for it

Fitness decides more than age does. Age still counts. The head and neck analysis found the benefit of chemotherapy fading as patients got older, and many teams are cautious beyond 70. What the oncologists look at is listed below. A patient who falls short is not abandoned. Radiotherapy alone, radiotherapy with a gentler drug, or a shorter course remain, and for some the honest advice is that the gain from adding chemotherapy is too small to justify what it would take out of them.

  • Up and about for more than half the day, and able to look after yourself.
  • Kidney function good enough for cisplatin, measured by a blood test and sometimes a formal clearance test.
  • Hearing tested beforehand where cisplatin is planned. Existing hearing loss or tinnitus points to another drug.
  • Blood counts, liver tests and heart function within limits.
  • Weight stable or supported. Patients who have lost more than a tenth of their weight see a dietitian before the start.
  • Someone with you. This treatment is hard to get through alone in a foreign city.

Supportive care that keeps treatment on schedule

The best predictor of finishing chemoradiation on time is what is set up before it starts. A dentist checks and treats the teeth before head and neck radiotherapy, because extractions afterward heal badly. A feeding tube is placed in advance, or a plan made to place one, for anyone whose throat will be in the field. A port or a PICC line saves the veins. Anti-sickness drugs come before each infusion and go home with you, cisplatin goes in with several hours of intravenous fluid to protect the kidneys, and a weekly blood test decides whether the next dose is given in full, reduced or delayed. A dietitian and a speech and swallowing therapist see head and neck patients through the course, since those who keep swallowing during treatment swallow better a year later.

Preparation of this kind takes ten to fourteen days.

Why missed days matter

Tumor cells that survive the first weeks multiply faster, a course stretched by gaps gives them time, and in head and neck and cervical cancer in particular, prolonging the overall treatment time lowers the cure rate. Breaks for side effects are sometimes unavoidable. Breaks for travel, holidays or paperwork are not, and a patient from abroad should arrive with visa, accommodation and companion arranged for the whole period.

Come to the emergency department at once
A temperature of 38 degrees or higher, shivering, or feeling suddenly unwell at any time during treatment and for two weeks after it. With low white cells, an infection can become life-threatening within hours, and it is treated with intravenous antibiotics the same night. Also come for vomiting that stops you drinking, passing very little urine, diarrhea more than six times a day, bleeding, or chest pain. The emergency department and both oncology teams are in the same hospital.

The drugs you are likely to meet

Cisplatin goes in as a drip, either once a week or once every three weeks, in head and neck, cervical and lung cancer. Carboplatin with paclitaxel, a weekly drip, serves the esophagus and the lung, fluorouracil runs as a continuous infusion through a small pump for four or five days, and capecitabine, its tablet form, is taken twice a day on radiotherapy days. Mitomycin takes one injection. Temozolomide comes as a capsule taken every day, weekends included, from the first to the last day of brain radiotherapy. Hair loss from these regimens is slight or absent, apart from the area of scalp inside a brain radiotherapy field.

How does chemoradiation fit with surgery, immunotherapy and other chemotherapy?

Before surgery
In rectal and esophageal cancer, chemoradiation comes first and surgery follows six to twelve weeks later. You can go home in between, and the operation can be done in either country.
After surgery
In head and neck cancer with positive margins or spread outside a lymph node, in some stomach and cervical cancers, and in glioblastoma, chemoradiation starts four to six weeks after the operation, once the wound has healed.
In place of surgery
For the larynx, bladder, anus, cervix and esophagus. A scan and an endoscopy two to three months afterward show whether the tumor has cleared, and surgery remains available if it has not.
Followed by more drug treatment
Glioblastoma patients continue temozolomide for six monthly cycles, and eligible stage III lung cancer patients now go on to a year of immunotherapy. Your oncologist at home can give both from a written protocol.

What do the weeks in Istanbul look like?

Ten to fourteen days before the first session
Joint consultation with the radiation oncologist and the medical oncologist. Tumor board. Blood tests, kidney function, hearing test, dental check, dietitian. Planning CT with mask or cushion. Line or port placed. Feeding tube if advised. Five to ten working days of radiotherapy planning.
Weeks one and two
Radiotherapy every weekday, chemotherapy on its scheduled day. People feel close to normal at this stage and wonder what the warnings were about, and that is when the warnings need repeating.
Weeks three and four
Soreness, tiredness and loss of appetite build. Pain relief is stepped up, food is changed to soft or liquid, and the feeding tube begins to earn its place.
Weeks five to seven
The hardest stretch. Weekly review becomes twice weekly where needed. Some patients spend a few nights in hospital for fluids or pain control, without interrupting radiotherapy.
The two weeks after the last session
Reactions peak about ten days after the end and then heal quickly. Blood counts recover. This is the period in which patients are most tempted to fly home and least fit to.

This table scrolls sideways on a narrow screen. Swipe or drag to see every column.

A typical week with weekly cisplatin
Day Radiotherapy Everything else
Monday Session Blood tests. Review by the radiation oncologist and nurse.
Tuesday Session Chemotherapy day. Fluids before and after the drip, five to six hours in the day unit.
Wednesday Session Dietitian. Swallowing therapist for head and neck patients.
Thursday Session Free, apart from anti-sickness tablets and drinking two liters.
Friday Session Review by the medical oncologist. Supplies for the weekend.
Saturday and Sunday Rest Temozolomide and capecitabine patients follow their own tablet schedule.
Tell us before treatment is planned
Kidney disease, hearing loss or tinnitus, heart failure, a pacemaker, numbness in the hands or feet, hepatitis B or C, HIV, pregnancy or any chance of it, earlier chemotherapy or radiotherapy with the records, and every medicine and supplement you take. Some herbal products interfere with chemotherapy and should stop.

This table scrolls sideways on a narrow screen. Swipe or drag to see every column.

How long to plan for
Cancer Radiotherapy Whole stay, with preparation and recovery
Head and neck 6 to 7 weeks 10 to 11 weeks
Cervix 5 to 5.5 weeks, then brachytherapy, all within 8 weeks 10 to 11 weeks
Lung, stage III 6 to 6.5 weeks 9 to 10 weeks
Glioblastoma 6 weeks 8 to 9 weeks
Rectum, before surgery 5 to 5.5 weeks 7 to 8 weeks
Bladder, anus, esophagus 4 to 6.5 weeks 7 to 10 weeks

What decides the cost?

Two departments bill for chemoradiation, and quotes that show only one of them mislead. On the radiotherapy side the price follows the number of sessions and the complexity of the plan, as it does for any course. On the chemotherapy side it follows the drug, the number of cycles, the day-unit time and the supportive drugs, and cisplatin costs far less than carboplatin with paclitaxel or a course of temozolomide. Then come the items that belong to neither department. A port or PICC line, a feeding tube, dental treatment, the hearing test, weekly blood tests, dietitian and swallowing therapy, and brachytherapy for cervical cancer are each priced. Nights cost extra. Any admission for fluids, pain control or a fever is charged as it arises, and with this treatment a family should budget for the possibility. Ten weeks of accommodation for two people is, for many families, the largest single line. Your own health moves all of it, since diabetes, kidney impairment, heart disease and weight loss before the start each add monitoring and admissions.

Radiotherapy packages published by hospitals in Istanbul list sessions, consultation, interpreter and transfers, and leave chemotherapy, admissions and hotel outside. Ask for one written quote. It should cover both departments, name the drug, state the number of cycles, estimate supportive care and give the daily rate for an unplanned admission.

A figure for you follows the free joint review of your file, and nothing before that review deserves the name.

What about language, companions and care once I am home?

A stay of this length needs settling into. One coordinator from the international patients team is assigned from your first message and remains your contact to the end. The team works in English, Arabic, French, Russian, Serbian, Romanian and Spanish, and arranges interpreting in other languages on request. The invitation letter naming the hospital and the treating doctor is sent about ten days before travel, and you should check that your visa covers ten to eleven weeks or can be extended from inside Turkey. Settle that early. The international patients office arranges the airport transfer, an apartment or hotel for you and a companion, and the daily transport, and an apartment with a kitchen near the hospital is the better choice, because by week four most patients eat only what can be prepared for them. Rooms for admitted patients have a companion bed. The hospital kitchen prepares halal, vegetarian and diabetic meals and the soft and liquid diets this treatment calls for. A prayer room is on site. A request for a female doctor is passed to the department and met wherever the rota allows.

Bring a companion who can stay.

Back home, the coordinator stays reachable on the same WhatsApp number. You leave with a radiotherapy summary listing every dose, a chemotherapy summary with drugs, doses and dates, the blood results from the final week, and a letter setting out the follow-up, which for most cancers means a response scan eight to twelve weeks after the end. Fever in the first two weeks after you return is still an emergency. Do not wait. Go to a hospital and show them the chemotherapy summary.

Chemoradiation FAQ

Is chemoradiation harder than radiotherapy alone?
Yes. Radiation reactions come earlier and are more severe, and the chemotherapy adds nausea, tiredness, low blood counts and drug-specific effects. In lung cancer trials, severe inflammation of the gullet rose from 4 to 18 percent with concurrent treatment.
How much does adding chemotherapy improve survival?
By 6.5 percentage points at five years in head and neck cancer, 6 points in cervical cancer and 4.5 points in stage III lung cancer compared with sequential treatment. In glioblastoma, two-year survival rose from 10.4 to 26.5 percent.
How long will I be in Istanbul?
Seven to eleven weeks depending on the cancer. That covers ten to fourteen days of preparation, four to seven weeks of treatment and about two weeks of recovery before flying.
Will I lose my hair?
With the drugs used alongside radiotherapy, hair loss is slight or absent. Hair does fall inside a radiotherapy field on the head.
Can I go home between treatments?
No. Radiotherapy is given every weekday, and gaps lower the chance of cure. The exception is the interval between chemoradiation and surgery in rectal or esophageal cancer.
Can my family stay with me?
Yes, and one person should. The international patients office arranges an apartment or hotel for the whole stay, and rooms for admitted patients have a companion bed.

References

  1. Pignon JP, le Maitre A, Maillard E, Bourhis J; MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiotherapy and Oncology. 2009;92(1):4-14.
  2. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. Journal of Clinical Oncology. 2008;26(35):5802-5812.
  3. Auperin A, Le Pechoux C, Rolland E, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. Journal of Clinical Oncology. 2010;28(13):2181-2190.
  4. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New England Journal of Medicine. 2005;352(10):987-996.
  5. James ND, Hussain SA, Hall E, et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. New England Journal of Medicine. 2012;366(16):1477-1488.

Editor's note

Written by the Biruni Hospital medical editorial team. Reviewed by Prof. Dr. Özcan YILDIZ, Medical Oncology.

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