Acupuncture for Dysphagia after Chemoradiation Therapy in Head and Neck Cancer: A Case Series Report

Abstract

Background

Dysphagia is a common side effect following chemoradiation therapy (CRT) in head and neck cancer (HNC) patients.

Methods

In this retrospective case series, ten HNC patients were treated with acupuncture for radiation-induced dysphagia and xerostomia. All patients were diagnosed with stage III/IV squamous cell carcinoma. Seven of 10 patients were percutaneous endoscopic gastrostomy (PEG) tube-dependent when they began acupuncture. Manual acupuncture and electroacupuncture were used once a week.

Results

Nine of 10 patients reported various degrees of subjective improvement in swallowing functions, xerostomia, pain and fatigue levels. Six (86%) of 7 PEG tube-dependent patients had their feeding tubes removed after acupuncture, with a median duration of 114 days (range 49–368) post CRT. One typical case is described in detail.

Conclusions

A relatively short PEG tube duration and reduced symptom severity following CRT were observed in these patients. Formal clinical trials are required to determine the causality of our observations.

Introduction

Head and neck cancer (HNC) accounts for 4% to 5% of all cancer diagnoses, with 42,000 new cases and 12,000 deaths each year in the United States.

Advances in radiation with concomitant chemotherapy, chemoradiation therapy (CRT), have resulted in significant improvement in survival rate and preservation of organ function in HNC patients(1, 2), and many patients are now cured with aggressive therapy(3–5). However, treatment of HNC with CRT is associated with significant toxicity and side effects. Acute toxicity includes mucositis, nausea/vomiting, dehydration, malnutrition, weight loss, pain, and leukopenia; long-term side effects are xerostomia (dry mouth), fibrosis and associated trismus, which all contribute to dysphagia(6–11). Due to the high incidence of grade 3–4 mucositis following CRT, patients are often not able to be fed orally leading to severe weight loss and malnutrition. Consequently, standard care employs a percutaneous endoscopic gastrostomy (PEG) tube during radiation for the majority of patients in order to provide adequate nutritional supply.

Dysphagia, or difficulty with swallowing, is a very common side effect following CRT in patients with HNC. Dysphagia has been reported to occur in up to 50% of patients after CRT and this number is considered by some to be underestimated(9, 12, 13). At 3 and 12 months following completion of CRT, 73% and 19% of patients are reported to still be PEG dependent(14). Dysphagia may lead to aspiration, which may significantly impact many aspects of health and quality of life in patients recovering from CRT. Although swallowing therapy has been found to improve dysphagia and reduce aspiration rate, many patients still have significant swallowing problems and remain PEG tube dependent for many months after completion of CRT(13, 15). The reported median PEG tube duration ranges from 178–365 days(16–18). The median PEG tube duration following CRT has been reported to be 5 months(14, 19). In general, swallowing issues continue to evolve during the first twelve months after CRT because of the delayed effect of the toxicity of the treatment, which includes gradual fibrosis of the pharyngeal muscles and soft tissues, persisting xerostomia, and damaged swallowing muscles. A number of studies suggest that swallowing function for HNC patients fails to improve 12 months after radiation therapy (15, 20, 21).

There are 3 published studies from China that have characterized the responses of HNC patients with dysphagia to acupuncture, including one non-randomized controlled trial (n=38)(22), and two case series (n=120 and n=11, respectively) in nasopharyngeal and esophageal cancers(23, 24). In addition to HNC-related dysphagia, a significant body of literature exists that characterizes the efficacy of acupuncture for stroke-related dysphagia(25–28). In this paper, we report a case series of 10 HNC patients treated at Dana-Farber Cancer Institute (DFCI) using acupuncture. The results suggest a need to more definitively evaluate the safety and benefits of acupuncture for HNC patients.

Case Summaries

We report on a group of 10 patients who have been treated with acupuncture for dysphagia and/or xerostomia at Zakim Center for Integrative Therapies at DFCI from October 2004 to May 2007.

This group of patients consists of 9 white males and 1 white female, with a mean age of 56 (range 29–78). All ten patients were diagnosed with stage III/IV squamous cell carcinoma of the head and neck. The primary tumor sites were located at the base of the tongue, the floor of the mouth, or tonsillar area.

Nine out of 10 patients received combined chemoradiation therapy. The chemotherapy was a carboplatin/Paclitaxel combination in six patients and a cisplatin based protocol in three. The remaining patient received radiation therapy alone. All 10 patients received radiation with a median dose of 7,000 cGy (range 6000–7200). Prior to or following CRT, 4 out of 10 patients had a primary tumor dissection. PEG tubes were needed in 9 of 10 patients during CRT and 7 were still PEG tube-dependent when they first entered acupuncture. Three out of 10 patients received esophageal dilation procedures due to strictures found by modified barium swallow (MBS) results. Among these 3 patients, 2 had received 5 and 2 dilations respectively, before starting acupuncture.

Four of 10 patients started acupuncture while still undergoing CRT and 6 received acupuncture after the completion of CRT. The median time of initiating acupuncture relative to the last day of CRT was 27 days (range −44 to 582).

At the first acupuncture visit, all patients complained of a wide range of symptoms including nausea/vomiting, anxiety, pain, fatigue, dysphagia and xerostomia, with the latter being the most frequent complaint. Most were undergoing swallowing therapy. All patients received acupuncture treatments for a median of 13.5 sessions (range 7–40). A typical visit interval was once a week or once every two weeks for at least 6 sessions. Manual acupuncture and electroacupuncture were used based upon the sensitivity and tolerability of the patient towards acupuncture stimulation. The needling sites of acupuncture were divided into two stages based on the timing of acupuncture and CRT: for patients who started acupuncture while undergoing CRT, no radiation field was needled. The needling sites were mostly located either on the four limbs or on the upper half of the head above the horizontal line of the eyes. Blood neutrophil, platelet counts and hemoglobin levels were monitored prior to each acupuncture session. For patients who started acupuncture 30 days post CRT, additional sites located around ears, neck, check, and jaws were often used: ST36, SP6, LI2, LI11, GV20, Shenmen/ear, Sanjiao/ear, ST7, ST6, ST5, CV23, GB20, Yintang (Figure 1). Actual points used on each patient varied based upon specific complaints of each patient at the time of each visit.

Figure 1.

Acupuncture points used in patients with head and neck cancer

Disposable acupuncture needles (VINCO™, Helio Medical Supplies, Inc. USA) 36–32 gauge, 1–1.5 inches (0.20–0.25 × 25–40 mm) were used. A ‘De Qi’ sensation, experienced by the patient as a deep and dull muscle ache at the site of the needle insertion (29), was attempted but often not necessarily achieved due to the sensitivity of patients. Electrostimulation sites were at GV20 and Yintang (Model: AWQ-104 L, Mayfair Medical Supplies Ltd., Hong Kong), with a frequency of 2–4 Hz. An Infrared heat lamp (Model: TDP CQ-27, Lhasa OMS, Inc. USA) was often used above the legs of patients during the session. Needles were retained at sites for 30 minutes in each session. Table 1 shows the summary table of these patients.

Table 1.

Patient characteristics and acupuncture responses

Patient No.	Sex	Age	Tumor Type	Primary Site	Stage	Chemo agents	RTa Dose(cGy) at primary site	Days from acupuncture initiation to LDRTb	Days from LDRT to PEG removal	Subjective acupuncture responses
1	M	78	SCCc	BOTd	T2, N1, M0	Carbo/Paclitaxel	7000	263	368	Able to swallow meat
2	M	54	SCC	TPe	T2, N3, M0	Carbo/Paclitaxel	6000	(26)f	NRg	Improved in xerostomia
3	M	59	SCC	BOT	T1, N2A	Carbo/Paclitaxel	7000	582	PEG remaining	Transient improvement in sleep
4	M	58	SCC	BOT	T4, N2b	TPFh	7000	(44)	100	Had less than expected toxicity
5	M	45	SCC	unknown primary	T1,N0	None	6400	5	No PEG used	Had less than expected toxicity
6	M	29	SCC	FOMi	T4, N1	TPF	Unknown	238	NR	Improved in insomnia, anxiety
7	M	73	SCC	BOT	T1, N2b	Carbo/Paclitaxel	7000	(34)	127	Transient improvement in fatigue level
8	F	52	SCC	TP	T1, N2a	Carbo/paclitaxel	6996	49	98	Improved in xerostomia and swallowing
9	M	66	SCC	TP	T3, N2c	Carbo/Paclitaxel	7200	49	127	Improved in xerostomia, swallowing, and neck pain
10	M	46	SCC	TP	T2, N2b	Cisplatin	6400	(38)	49	Improved in anxiety, insomnia, and xerostomia

^aRT: radiation therapy

^bLDRT: last day of radiation therapy

^cSCC: Squamous cell carcinoma

^dBOT: base of tongue

^eTP: tonsillar pillar

^fDays of acupuncture initiated prior to end of RT

^gNR: not relevant; PEG was removed before the initiation of acupuncture

^hTPF: Docetaxel, Cisplatin, 5-Fluorouracil

ⁱFOM: floor of mouth

After acupuncture, nine of 10 patients reported various degrees of subjective improvement in swallowing functions, xerostomia, pain and fatigue levels. Of seven patients with PEG tubes, one started acupuncture 528 days after CRT and did not respond to acupuncture, as defined by a PEG tube removal following acupuncture treatment. The patient later received a tracheotomy and was still PEG tube-dependent at the time of writing this report. The remaining 6 patients all had their PEG tube removed. Table 2 shows the number of days the PEG tube remained in place in relationship to the end of CRT and the initiation of acupuncture treatment. No adverse event related to acupuncture was observed in any patient.

Table 2.

Mean and median PEG durations in patients with PEG removed after acupuncture

	n	Mean(days)	SD	Median(days)	range
Total PEG durationa	6	206	115	173	98–429
Post-CRT PEG durationb	6	145	113	114	49–368
PEG duration between acupuncture and removalc	6	104	42	96	49–161

^aTotal PEG duration: days from initial PEG placement to the removal

^bPost-CRT duration: days from last days of CRT to the removal

^cPEG duration between acupuncture and removal: days from first day of acupuncture to the PEG removal

Case Vignette

A 78-year-old white male patient developed a mass on the left side of his neck in September 2005. Examination found a 2 × 2 cm lesion on the left tongue base extending into the vallecula and a neck mass measured 1.5 cm in size located at left upper jugulodigastric region. The biopsy report was consistent with poorly differentiated invasive squamous cell carcinoma. He was staged as a T2, N1, M0 stage III squamous cell carcinoma of left tongue base.

On December 1, 2005, the patient underwent concurrent chemoradiation therapy with carboplatin AUC dose of 1.5 and Paclitaxel at 45 mg/sqm, along with daily radiation therapy. A PEG tube was placed prior to chemoradiation therapy. The patient received periodic nutritional consultations as well as speech and swallowing therapy to support swallowing function and nutritional needs at the beginning of chemoradiation therapy, which was completed on January 30, 2006. The patient received two esophageal dilation procedures for dysphagia during the 2^nd and 5^th month post CRT, respectively. He continued speech and swallowing therapy until October 11, 2006, 9 months post-chemoradiation therapy. At that time, the patient was eating small amount of food by mouth three times per day and taking four cans of liquid food via PEG. He still had significantly decreased appetite, taste and xerostomia. He was discouraged by the lack of progress in his swallowing function. The speech and swallowing therapist had concluded that the patient had not shown significant changes in his swallowing function. His weight was down 2.3 kg during the past one month. The patient was referred to try acupuncture by the swallowing therapist to increase saliva and possibly improve his taste and appetite. The acupuncture-naive patient started the first acupuncture treatment on October 20, 2006. At the initial treatment, he rated his xerostomia at 5 out of 10, and lack of taste of food at 10 out of 10. The patient was naive to acupuncture. Therefore, thinner acupuncture needles (Seirin®, Japan) (0.16 × 30 mm) were used at his first the visit. The following acupuncture points were used: LI2, LI4, Yintang, ST7, ST5, ST6, Sanjiao/ear, GV 20 and GV 24. At the second visit, the patient reported a slight improvement in taste of food. During subsequent treatments, electroacupuncture stimulation was added along with additional acupuncture points: CV23, ST36, SP9, SP6. The size of acupuncture needles was changed to 0.20 × 40 mm, with intent to produce De Qi sensation. The stimulation was administered to Sanjiao/ear and ST5 on the right side with a low frequency (4–5 Hz) and a continuous wave pattern at a level that was well-tolerated by the patient. At the third visit, the patient reported that he could eat more food with improved swallowing. The patient was encouraged by the improvement he noticed. He was able to increase varieties of food such as Jelly Stick, Sushi and clam meat. At the 10th visit, the patient had reduced reliance on liquid food by 50% and gained weight. During Thanksgiving, 4 weeks after starting acupuncture, he was able to eat "almost everything" except turkey meat. At the 15th visit, the patient reported a significant increase of salivary production for which he was able to “lick envelopes”. He still had some trouble swallowing meat. He also noted continued improvement in the food taste since beginning acupuncture. At the 16th visit, January 10, 2007, he reported he could chew and swallow 60%-70% of pork, beef and turkey and discontinued using PEG. On January 22, 2007, at the follow-up nutrition consult, he weighed 87.5 kilogram and had gained 1.5 kg in three months. His 18^th and final acupuncture session was performed on January 27, 2007. The PEG tube was removed on February 2, 2007, three months after starting acupuncture. The patient is still being followed by treating oncologists with a satisfactory swallowing function and a disease-free status in 2009.

Discussion

In this retrospective case report, head and neck cancer patients undergoing chemoradiation treatment received multiple sessions of acupuncture treatment aiming to alleviate dysphagia and xerostomia symptoms. Acupuncture intervention appeared to be well-received and well-tolerated by this group of patients. Most patients reported subjective improvement in their swallowing function with a shorter-than-average PEG tube duration after CRT, based on previously published reports and our clinical experience. However, without prospective and comparative studies, the benefits of acupuncture for dysphagia in this population can not be definitively established.

The entire duration of PEG and the PEG duration post CRT are important indicators of dysphagia in patients undergoing CRT. Previous studies in a similar population reported median PEG durations ranging from 178 to 365 days;(16–18, 30) the reported median post-CRT PEG duration ranged from 147 to 150 days(14, 19). The median duration of PEG in our group is slightly lower that what Wiggenraad reported (173 vs. 178 days).(17) However, the post-CRT PEG duration in our group is much shorter than Nguyen’s report (median:114 vs. 150 days; mean:145 vs. 240 days)(19). It is possible that the smaller differences in PEG durations between our cohort and other published reports results from different chemoradiation protocols. However, a 22% shorter median post-CRT PEG duration in our acupuncture-treated cases is unlikely to be due only to variations in CRT regimes, and it is possible that this difference is due in part to acupuncture interventions.

Some preliminary evidence suggests that the mechanism through which acupuncture impacts dysphagia by improving salivary production, restoring swallowing reflex, and inhibiting the fibrosis process.

Xerostomia, or dry mouth, is considered a significant factor underlying dysphagia(31). Several pilot clinical studies suggest that acupuncture may improve xerostomia caused by radiation therapy in patients with head and neck cancers(32–37). Johnstone found that acupuncture produced a 70% response rate of increasing 10% or more from the baseline as assessed using the Xerostomia Inventory(32, 33). Wong reported a phase I-II study with transcutaneous electrical stimulation. Forty-six patients were randomized among three groups with different acupuncture points. After 6 weeks of treatment, for 37 patients who completed the treatment course, salivation production was statistically significantly increased from baseline in all three groups at both 3- and 6- months(34, 35). A pilot fMRI study found a relationship between stimulating an acupuncture point, LI-2, located at the base of index finger, and the activation of the brain function area that is responsible for salivary production, suggesting a central neural pathway involvement(38).

One study used swallowing electromyography to detect the effect of acupuncture on swallowing related muscles and evoked potentials in the brainstem in a group of chronic post-stroke patients with moderate to severe dysphagia(n=30) (39). Acupuncture needles were inserted into four acupuncture points located around the neck area. The test was performed 5 min before and 5 min after acupuncture treatment. The study found that the amplitude and time limit of cricothyroid muscle, and time limit of tongue muscles in the patients with bulbar palsy significantly decreased after acupuncture. Similar studies have not yet been conducted in head and neck cancer patients recovering from CRT.

Conclusions

In summary, we report a case series of ten head and neck cancer patients with complaints of dysphagia and other related symptoms after chemoradiation therapy. All were treated with multiple sessions of Chinese acupuncture, manual and electro-stimulation at classical locations of acupuncture. The clinical intentions of the intervention were to reduce local pain, stimulate salivary production, and stimulate local nerve sensory receptors of related cranial nerves (namely VII, IX, X, XI and XII nerves).

We observed a short PEG duration following CRT in these patients treated with acupuncture, along with other subjective improvement in pain, fatigue and xerostomnia symptoms. However, formal clinical trials are required to determine the causal relationship between acupuncture and swallowing function in this population. We have initiated a randomized controlled trial of acupuncture in this population to collect safety, feasibility and preliminary efficacy data.