|Ahead of print publication
Synchronous thoracic and head-and-neck malignancies-double trouble-challenges, pitfalls, and lessons learnt
Kanika Sharma Sood, Manisha Himthani, Aditi Tanwar, S Lakshmana Perumal
Department of Radiotherapy, Dharamshila Narayana Superspeciality Hospital, New Delhi, India
|Date of Submission||30-Dec-2018|
|Date of Acceptance||11-Jun-2019|
|Date of Web Publication||13-May-2020|
Kanika Sharma Sood,
Department of Radiotherapy, Dharamshila Narayana Superspeciality Hospital, Vasundhara Enclave, New Delhi - 110 096
Source of Support: None, Conflict of Interest: None
Synchronous malignancies arising from head and neck and thorax are rare presentation, and only few cases are reported in the scientific literature. We report three cases of double primary malignancies treated at our hospital.
Keywords: Double malignancy, radiation dual malignancy, synchronous malignancy
|How to cite this URL:|
Sood KS, Himthani M, Tanwar A, Perumal S L. Synchronous thoracic and head-and-neck malignancies-double trouble-challenges, pitfalls, and lessons learnt. J Can Res Ther [Epub ahead of print] [cited 2021 Nov 29]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=284266
| > Introduction|| |
With the advent of imaging techniques such as positron emission tomography-computed tomography (PET-CT) scans, it is not infrequent to detect multiple synchronous cancers. Especially, there is a high risk of field carcinogenesis in the aero-digestive tract., The frequency of multiple primary tumors overall is 2%–17% across the literature.,,
Treatment of such tumors is challenging, especially when radiation therapy (RT) has to be delivered. The dilemmas in these cases include sequencing of RT and inclusion or omission of concurrent chemotherapy. There are also challenges in appropriate treatment delivery which include appropriateness of immobilization and simulation, choice of treatment techniques, and managing the toxicities of such magna-field therapies.
The pitfalls include uncertainties in treatment delivery in such magna-field therapies.
We describe the challenges and learnings in three cases where synchronous radiation to thoracic and head-and-neck cancer was delivered simultaneously.
| > Case Reports|| |
Case 1: Synchronous carcinoma breast and carcinoma tongue
The patient presented with nonhealing ulcer on the left lateral border tongue. On evaluation it was diagnosed as carcinoma tongue. She underwent surgery (hemiglossectomy with no lymph node dissection) at an outside center. She received no adjuvant treatment and within 2 months, she noted a lump in the right breast which on investigations was found to be infiltrating ductal carcinoma of the breast. She underwent modified radical mastectomy and was on adjuvant chemotherapy when she noted swelling in the left neck which was found to be squamous cell carcinoma. She underwent modified radical neck dissection and was referred to our center for adjuvant treatment.
As per histopathological parameters, it was not judicious to delay radiation at either of the sites; hence, both sites received RT simultaneously. She was simulated with arm above head abducted away from the neck and planned a dose of 50 Gy/25 fractions/5 weeks to chest wall and supraclavicular fossae and 66 Gy/33 fractions/6.5 weeks to the left side neck by volumetric arc therapy (VMAT) technique in image guidance[Figure 1] and [Figure 2]. She was not given concurrent chemotherapy despite extra nodal disease. She completed her entire treatment in planned duration with manageable hematotoxicity, Grade II mucositis, and Grade II cutaneous toxicity.
Case 2: Synchronous carcinoma tonsil and carcinoma esophagus
The patient was investigated for odynophagia and dysphagia and was found to have mid-esophageal carcinoma with synchronous carcinoma in the left tonsil.
The options of surgery for carcinoma of esophagus followed by radiation to the tonsillar malignancy were considered. However, the patient was asymptomatic for esophageal disease, and the delay also carried the risk of progression of disease at tonsil. Hence, he was planned for concurrent chemoradiation to face and neck and chest, but he denied chemotherapy. He was simulated supine with arms by side for head and neck and supine with arms above head for esophageal lesion. Separate plans were created, but summation plans were made to determine lung doses. Both sites were treated simultaneously by intensity-modulated RT (IMRT) in image guidance to a dose of 70 Gy in 35 fractions in 7 weeks to face and neck and 50.4 Gy in 28 fractions in 5.5 weeks to chest [Figure 3] and [Figure 4]. The patient tolerated the treatment moderately with a treatment interruption of 5 days due to esophagitis for which he required nasogastric tube insertion. On response evaluation at 3 months, he had a complete remission on both sites.
Case 3: Synchronous carcinoma base of tongue and carcinoma esophagus
The patient was evaluated for odynophagia and was diagnosed with carcinoma base of tongue. PET-CT for metastatic workup revealed synchronous carcinoma esophagus (squamous cell carcinoma). He was treated with concurrent chemoradiation to both the sites after a multimodality discussion. He was simulated supine with arms by side for head and neck and supine with arms above head for esophageal lesion. Separate plans on different structure sets were created. However, summation plans were made to determine lung doses. RT was delivered by IMRT in image guidance to a dose of 72 Gy/36 fractions in 7 weeks to face and neck and 50 Gy in 28 fractions in 5.5 weeks to esophageal lesion [Figure 5] and [Figure 6]. He developed febrile neutropenia (Grade 4) which was appropriately managed but contributed to a treatment break of 15 days. On response evaluation at 3 months, he achieved complete remission of disease at both sites.
| > Discussion|| |
The incidence of multiple primary cancers is rare and is reported to be between 0.3% and 4.3%. Double primary malignancies could be divided into two categories, depending on the interval between tumor diagnoses. Synchronous malignancies are those where the second tumor occurs either simultaneously or within 6 months after the first malignancy, whereas metachronous malignancies are those where second tumors develops after 6 months or more than the first malignancy. The association between synchronous primary tumors in the aero-digestive tract is a well-known phenomenon that has been explained by the concept of “field cancerization.” The mucous epithelium of the head and neck, lung, and esophagus is exposed to common carcinogenic agents, leading to multiple carcinomas in these regions. Strong epidemiological evidence suggests tobacco as the main carcinogen and alcohol as a promoter of carcinogenesis. The incidence of synchronous cancers in patients with esophageal cancer ranges from 3.6% to 27.1%. Majority of the synchronous cancers are in the head-and-neck regions.
Positive association between alcohol intake and carcinoma of the breast has been observed. The risk appears to be linearly related to the amount of alcohol consumed. Alcohol and tobacco are considered to be the major etiological factors in the development of esophageal carcinoma worldwide.
Features indicating the possibility of a second primary tumor can include
- Unusual site of metastatic spread not explained by natural disease history
- Mismatch of tumor burden and tumor marker levels
- Solitary metastasis
- New metastasis occurring several years after successful cancer treatment
- Suspicion of secondary malignancy in patients with prior radiation
- Suspicion of hematological malignancy after prior chemotherapy
- Differential standard uptake value of suspected lesions on PET-CT.
In case of a suspected secondary primary, a histological confirmation should be pursued, if the patient is considered for active treatment. With the advances in imaging and imaging-guided biopsy techniques, it is in most cases possible to get enough tissue for an adequate diagnosis.
Management of synchronous cancers is always case specific and there are no defined guidelines. For the majority of situations of patients with synchronous multiple primaries, only case reports are available in the literature, and these should be applied to an individual clinical situation with caution. There is not enough literature or case reports suggesting the use of such “Magna-field radiation.”
Apart from stage of disease, the patient's performance status, likelihood of morbidity, and prevention of delay of treatment should be considered while formulating the line of management. Patients with synchronous multiple primaries should be discussed in multidisciplinary team (MDT) meetings, and a consensus on a therapeutic strategy can sometimes take ≧1 MDT to form. Furthermore, the patient should be informed about the situation and therapeutic challenges, and often, the uncertainty about the prognosis, because the therapy approach needs to be adapted.
In localized disease, the strategy may be surgery or radiation/chemoradiation therapy covering both malignancies., Importantly, patients with active secondary malignancy are excluded from the vast majority of clinical trials involving novel treatments.
The radiation delivery is usually a complex process when treating dual sites simultaneously. It requires a diligent radiation planning and strict monitoring, as these treatments are technically demanding and expose the patient to a higher risk of side effects.
First and the foremost, it requires a judicious selection of treatment position, especially if target volumes are in close vicinity to each other. Radiation planning with conventional techniques carries the risks of uncertainties in delivering adequate dose and also exposes uninvolved organs to high doses of radiation. Treatment by conformal techniques including IMRT or VMAT in image guidance is preferable due to heterogeneous and large treatment volumes.
Close monitoring for toxicities, especially hematotoxicity due to large treatment field, is essential. Prophylactic colony-stimulating growth factors may be considered, especially where concurrent chemotherapy is delivered. Giving constraint to bone marrow may be helpful. However, it was not attempted in our cases, as it leads to poor dosimetry to heart and lung. Prophylactic placement of feeding tube should also be encouraged to prevent treatment interruptions.
De-escalation of therapy to facilitate completion of therapy and prevent treatment-related mortality should be strongly considered. As in our case, the patient who received concurrent chemotherapy had Grade 4 neutropenia which contributed to significant treatment interruption and morbidity.
Hence, the treatment of synchronous malignancy is surely a double trouble, but if done appropriately and with caution, it is surely doubly rewarding.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Suzuki T, Takahashi H, Yao K, Inagi K, Nakayama M, Makoshi T, et al.
Multiple primary malignancies in the head and neck: A clinical review of 121 patients. Acta Otolaryngol Suppl 2002;547:88-92.
Hulikal N, Ray S, Thomas J, Fernandes DJ. Second primary malignant neoplasms: A clinicopathological analysis from a cancer centre in India. Asian Pac J Cancer Prev 2012;13:6087-91.
Warren S, Gates O. Multiple primary malignant tumors: A survey of the literature and statistical study. Am J Cancer 1932;16:1358-414.
Bugher JC. The probability of the chance occurrence of multiple malignant neoplasms. Am J Cancer 1934;21:2309.
Moertel CG, Dockerty MB, Baggenstoss AH. Multiple primary malignant neoplasms. II. Tumors of different tissues or organs. Cancer 1961;14:231-7.
Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 1953;6:963-8.
Kagei K, Hosokawa M, Shirato H, Kusumi T, Shimizu Y, Watanabe A,et al
. Efficacy of intense screening and treatment for synchronous second primary cancers in patients with esophageal cancer. Jpn J Clin Oncol 2002;32:120-7.
Heroiu Cataloiu AD, Danciu CE, Popescu CR. Multiple cancers of the head and neck. Maedica (Buchar) 2013;8:80-5.
Zhang Z, Gao S, Mao Y, Mu J, Xue Q, Feng X, et al.
Surgical outcomes of synchronous multiple primary non-small cell lung cancers. Sci Rep 2016;6:23252.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]