A rare case report of colon metastasis from primary oropharyngeal squamous cell carcinoma treated with a combination of surgery, radiotherapy and immunotargeted therapy

Introduction

Background

We present the case of a 72-year-old male patient who underwent radical radiotherapy with concurrent chemotherapy for previously diagnosed oropharyngeal squamous cell carcinoma (OPSCC). After complaining of “diarrhea” during follow-up visits, he was re-examined. The positron emission tomography-computed tomography (PET-CT) findings confirmed colonic metastasis and axillary lymph node enlargement. After the surgical removal of the colon tumor, OPSCC metastasis was confirmed.

Rationale and knowledge gap

To date, only two cases of metastasis of OPSCC to the colon have been reported in the literature: one patient had multiple bone metastases combined with human immunodeficiency virus (HIV) infection, while the other patient was initially diagnosed with combined colonic metastases and underwent palliative surgery without radiotherapy and chemotherapy. Their disease characteristics differed from those of our patient.

Objective

Our patient first received radical radiotherapy with concurrent chemotherapy and consolidation therapy, achieving complete remission. He later presented with metastasis to the colon and axillary lymph nodes during follow-up visits. PET-CT findings of other organs and primary lesions did not suggest recurrence or metastasis. Thus, this case provides new references for the pattern of disease progression in patients with head and neck squamous cell carcinoma (HNSCC) after radical treatment. This patient achieved long-term, high-quality survival with local surgery, radiotherapy, systemic immune checkpoint inhibitors (ICIs), and anti-vascular targeted therapy. This regimen provides an important reference for the treatment of this condition. We present this case in accordance with the CARE reporting checklist (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-1744/rc).

Case presentation

The patient was a 72-year-old male. In December 2020, he attended Shandong University Qilu Hospital (Qingdao) complaining of a “foreign body sensation in the pharynx for more than 3 months”, and he received treatment for same. Electronic laryngoscopy on December 29, 2020 showed the following: The right tonsil was rough and uneven with a neoplasm and a bulge. Pathological studies of the biopsy sample indicated non-keratinizing squamous cell carcinoma.

The patient was later admitted to Qingdao Municipal Hospital and underwent a comprehensive head and neck magnetic resonance imaging and related imaging examinations. He was diagnosed with cT4N2M0 stage III HPV16 (+) (American Joint Committee on Cancer, 8th) squamous cell carcinoma of the right tonsil with bilateral cervical lymph node metastases. Due to the extent of the disease, he was treated non-surgically with definitive function preserving definitive chemoradiotherapy.

After confirming the absence of contraindications to treatment, radical radiotherapy with concurrent chemotherapy was planned. On January 15, 2021, the patient commenced cycle 1 of a paclitaxel liposome plus cisplatin chemotherapy regimen. Specifically, he was given 240 mg of paclitaxel liposome on day 1, and 60 mg of cisplatin on days 1 and 2 of the 21-day cycle. Volumetric modulated arc radiotherapy was performed from January 18, 2021 to March 3, 2021 to the following target areas: the gross tumor volume of the primary tumor (GTVp): the primary tumor in the oropharynx; the gross tumor volume of the lymph nodes (GTVnd): enlarged lymph nodes in the neck bilaterally; clinical target volume 1 (CTV1): the GTVp, the right Ib, II, III, and IV areas, and the lymph node drainage area in the left II and III areas; and CTV2: the lymph drainage area in the left IV area; the planning target volumes were as follows: PGTVp (planning gross volume of primary tumor): GTVp flared 0.3 cm; PGTVnd (planning gross volume of metastatic lymph nodes): GTVnd flared 0.3 cm; planning tumor volume 1 (PTV1): CTV1 flared 0.3 cm; and PTV2: CTV2 flared 0.3 cm. The prescribed doses were as follows: 95% PGTVp: 69.96 Gy/2.12 Gy/33 f; 95% PGTVnd: 69.96 Gy/2.12 Gy/33 f; 95% PTV1: 60.06 Gy/1.82 Gy/33 f; and 95% PTV2: 50.96 Gy/1.82 Gy/28 f.

The patient developed radiotherapy-induced Grade 2 (CTCAE 5.0) oral mucositis during radiotherapy and completed radiotherapy after receiving symptomatic treatment. Two cycles of cisplatin single-agent synchronized chemotherapy were given during radiotherapy as follows: 140 mg of cisplatin on day 1 of the 21-day cycle. One cycle of consolidation chemotherapy was administered on March 24, 2021 as follows: 240 mg of paclitaxel liposomal on day 1 plus 60 mg of cisplatin on days 1–2. Grade 4 leukopenia and Grade 3 thrombocytopenia occurred after chemotherapy but normalized after symptomatic treatment.

The patient later entered the follow-up phase. In July 2021, patient complained of lower abdominal pain with diarrhea and watery stools three times a day without obvious triggers. On July 20, 2021, PET-CT at Qingdao Municipal Hospital showed that the cecum and ascending colon proximal wall had obvious irregular thickening, accompanied by obvious abnormal hypermetabolism. The possibility of malignant lesions was considered high. The left axillary lymph nodes were enlarged (Figure 1,2). The patient was transferred to the General Surgery Department, and after excluding contraindications to surgery, radical resection of right hemicolectomy, intestinal adhesion release, chemotherapeutic drug infusion, and laparoscopic transurethral ureteral stenting were performed under general anesthesia on July 23, 2021.

Figure 1 ¹⁸FDG-positron emission tomography-computed tomography shows hypermetabolic colon and axillary lymph nodes.

Figure 2 ¹⁸FDG-positron emission tomography-computed tomography shows hypermetabolic colon.

The post-operative pathological results showed that the ileocecal part and the ascending colon were extensively infiltrated with heterogeneous cells from the plasma membrane to the mucous membrane with intraluminal tumor thrombus and nerve invasion. Cancer metastasis was visible in the peri-intestinal lymph nodes (11/14). Immunohistochemistry staining of the tumor cells showed the following: CK (+), P63 (+), P16 (+), CK5/6 (+), CK7 (+), CK20 (–), Ki67 (80%+), and PD-L1 combined positive score (CPS) <1. The clinical history and immunohistochemistry data were consistent with non-keratinizing squamous cell carcinoma metastasis (Figure 3).

Figure 3 Metastatic squamous cell carcinoma of the colon with tumor cells spreading from the plasma membrane surface, mostly in the muscularis propria (HE, ×40).

The patient was diagnosed with squamous cell carcinoma of the right tonsil with bilateral cervical lymph node metastases (cT4N2M0 stage III) after radiotherapy, colon metastases, and T4N2M1 stage IV lymph node metastases in the left axilla. He was admitted to oncology department after surgery and underwent six cycles of chemotherapy combined with immunotherapy from September 6, 2021 to January 6, 2022 as follows: 200 mg of penpulimab on day 1 plus 0.3 g of paclitaxel (albumin-bound) on day 1. The patient underwent a chest CT evaluation after two cycles of treatment, and the axillary lymph nodes showed a clinical complete response (cCR) (Figures 4,5). Later, from January 27, 2022 to July 26, 2022, the patient received eight cycles of penpulimab (200 mg) immuno-maintenance therapy, during which the cCR persisted.

Figure 4 Computed tomography shows left axillary lymphadenopathy at the baseline before first-line treatment. The arrow points to left axillary lymphadenopathy.

Figure 5 Computed tomography after first-line two-week-cycle therapy combined with immunotherapy shows complete response. The arrow points to shrunken axillary lymph node.

In August 2022, chest CT showed that the left axillary lymph nodes had enlarged compared to the previous CT scan and the efficacy evaluation indicated progressive disease (PD). On September 15, 2022, axillary lymph node volumetric curvilinear intensity-modulated radiotherapy was commenced to the following target areas: GTVnd: enlarged lymph nodes in the left axilla; CTV: GTVnd flared 1 cm due to suspicious small lymph nodes; and PTV: CTV flared 0.5 cm. The prescribed dose was as follows: 95% PTV 60 Gy/3 Gy/20 f. After radiotherapy, the axillary lymph nodes showed a cCR (Figures 6,7).

Figure 6 Computed tomography shows axillary lymphadenopathy at the baseline before radiotherapy. The arrow points to left axillary lymphadenopathy.

Figure 7 Computed tomography after radiotherapy shows complete response. The arrow points to shrunken axillary lymph node.

As the previous chemotherapy regimen had resulted in severe granulopathy and a drop in platelets, the patient refused to continue chemotherapy. The patient has been receiving penpulimab plus anlotinib since September 2022. The patient achieved progression-free survival (PFS) after first-line surgery, immune-combination chemotherapy, and second-line local radiotherapy. The patient has been receiving immune-combination targeted therapy for 28 months. We used a timeline figure to briefly summarize the diagnosis and treatment of this case (Figure 8).

Figure 8 Timeline figure to briefly summarize the diagnosis and treatment. PET-CT, positron emission tomography-computed tomography; cCR, clinical complete response; PD, progressive disease.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

International Multidisciplinary Team (iMDT) discussion

Discussion and opinions among physicians from the Oncology Department, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital).

Key findings

OPSCC is a type of HNSCC. Its prevalence has shown an increasing trend in recent years, mainly related to an increase in human papillomavirus (HPV) infection. The rate of metastasis from HNSCC is approximately 10–15% (1). The later the staging, the greater the chance of metastasis (1). The most common metastatic organs include the bones, liver, and lungs (2). Metastasis indicates a poor prognosis, with a 5-year survival rate of 15% (1). Metastasis of HNSCC to the colon and large intestines is very rare and have not been previously reported in China.

Comparison with similar studies

Only two cases of metastasis of OPSCC to the colon have been reported abroad: one patient had multiple bone metastases combined with HIV infection (3), and the other patient was initially diagnosed with combined colonic metastases and underwent only palliative surgery without radiotherapy or chemotherapy (4). Their disease characteristics differed from those of our patient. Our patient first received radical radiotherapy with concurrent chemotherapy and consolidation therapy, achieving a cCR. He later presented with metastasis to the colon and axillary lymph nodes during follow-up visits. PET-CT findings of other organs and primary lesions did not indicate recurrence or metastasis. This case provides a new reference for the pattern of disease progression in patients with HNSCC after radical treatment.

Explanations of findings

In some cases, patients with late-stage HNSCC, including OPSCC, can achieve satisfactory treatment results through surgery combined with chemotherapy and radiotherapy or radical radiotherapy with concurrent chemotherapy. However, approximately 50% of these patients develop recurrence or metastasis (1). Once distant metastasis occurs, the prognosis is extremely poor. Currently, systemic treatment is still the main treatment for local recurring or metastatic HNSCC.

For first-line treatment, immunotherapy and combination therapy with immunotherapy based on the expression level of PD-L1 can be adopted, but second-line treatment still lacks a standard approach. Previous basic research has shown that ICIs combined with antiangiogenic drugs exert mechanistically synergistic effects (5). Antiangiogenic drugs may enhance the efficacy of immunotherapy through mechanisms such as the normalization of tumor vasculature, enhanced therapeutic drug delivery, lymphocyte infiltration and migration, and enhanced antigen presentation. While ICIs can inhibit the vascularization of tumors through mechanisms that activate effector T cells, upregulate γ-interferon secretion, and elevate the density of tumor-infiltrating lymphocytes. The American Society of Clinical Oncology (ASCO) 2022 study reported the results of a single-arm, multicenter phase-II clinical trial of penpulimab in combination with anlotinib for the treatment of recurrent or metastatic HNSCC in patients who failed first-line platinum-containing chemotherapy; the trial included a total of 38 patients, with an objective response rate of 34.21% and a median PFS duration of 8.35 months, demonstrating promising efficacy.

Our patient received immunotherapy as first-line therapy, but due to obvious bone marrow inhibition after chemotherapy, the patient refused to continue treatment. Given the synergistic mechanism of ICIs and anti-vascular drugs, pegylated monoclonal antibody was administered across the line and combined with targeted therapy with anlotinib. The patient’s PFS with second-line therapy reached 14 months, and because the patient’s immune medication have been used in the first-line, we inferred that the patient had benefited from anlotinib therapy.

Studies on the efficacy of local treatment for recurring or metastatic malignant tumors have focused on tumors in the breast, lungs, and prostate. Currently, high-level evidence on the application value of local treatment for HNSCC is lacking. The literature suggests that positive local treatment can prolong the survival of patients with oligometastases from HNSCC (when the number of metastatic lesions is ≤5), especially if the primary tumor is well-controlled, resulting in increased survival benefits (6).

The PET-CT findings confirmed that this patient did not develop recurrence of local lesions and in the neck lymph nodes during follow-up, but the patient did develop metastasis in the colon and axillary lymph nodes. He underwent resection of the colonic mass and local radiotherapy of the axillary lymph nodes and later received systemic treatment to control progression. Currently, the patient continues to receive targeted therapy combined with continuous immunotherapy, and has shown no disease progression. The overall PFS has reached 28 months. Through positive local treatment combined with medication treatment, our patient achieved PFS for a long duration and achieved a cCR; therefore, this case provides a reference for patients with rare metastases to the colon.

Implications and actions needed

Our patient was re-examined because of severe diarrhea. Diarrhea is not a characteristic clinical manifestation of malignant tumors, such as recurring colon cancer or secondary malignant tumors of the colon. Clinical treatment of this condition is complicated. During follow-up visits, our patient presented with diarrhea and was ultimately diagnosed with metastasis of HNSCC to the colon. For patients with HNSCC, especially those with relatively late local staging, if digestive symptoms such as diarrhea, obstruction, hemorrhage, and perforation are observed during follow-up visits, the possibility of metastasis should be considered and endoscopy or PET-CT should be performed.

Several issues on the diagnosis and treatment of this patient require further discussion

This is the first case of colon metastasis from primary OPSCC treated in our hospital. So we have some further thoughts and questions about how to treat it, we discussed some of the current issues with Daniel T. Ginat and Yuvnik Trada. The contents are as follows.

Question 1: How should the value of local surgical resection for HNSCC with gastrointestinal metastasis be evaluated?

Expert opinion 1: Dr. Daniel T. Ginat

Based on clinicoradiologic outcomes, such as PFS and quality of life measures.

Expert opinion 2: Dr. Yuvnik Trada

The values of resection for palliation of symptomatic metastasis and for prevention of obstruction as in this case should be measured using patient reported quality of life measures. In oligometastatic setting, value of local resection for improving oncological outcomes should be measured with overall survival.

Question 2: How should the application value of anti-angiogenic drugs in advanced HNSCC be evaluated?

Expert opinion 1: Dr. Daniel T. Ginat

Based on imaging using RECIST criteria, including PET, CT, and/or MRI, as well as tumor genetics (7,8).

Question 3: How should the value of radiotherapy in the treatment of oligometastasis of malignant tumors be evaluated?

Expert opinion 1: Dr. Daniel T. Ginat

Via diagnostic imaging for tumor response and assessment for possible adverse effects.

Expert opinion 2: Dr. Yuvnik Trada

The incidence of HPV-associated OPSCC is increasing and represents a distinct disease process with better prognosis and different recurrence patterns compared to HPV non-associated OPSCC (9,10). In selected patients with metastatic HPV-associated OPSCC, relatively good 2 years disease-specific survival outcomes of 16% have been reported (11). Hence, a rationale exists for addition of local treatments to improve outcomes (12).

In metastatic setting, the value of local treatment should be primarily assessed through overall survival and patient-reported quality of life. Following oligometastatic treatment, secondary outcomes measures of PFS and time-off systemic therapy are also important endpoints.

Conclusions

We presented a very rare case of colonic metastasis of OPSCC. This case indicates that OPSCC may metastasize to the colon. Thus, when a patient suddenly presents with gastrointestinal symptoms, it is important to consider colonic metastasis. Currently, the standard comprehensive treatment of oligometastasis of HNSCC is unclear, and local treatment represents an important research direction for exploration in the future. Through surgery, radiotherapy, and medication treatment, our patient achieved PFS for 28 months and is still receiving treatment. The PFS duration of our patient is significantly longer than the currently reported median PFS duration of patients with metastatic HNSCC treated with medication alone (13). This case not only reports a real case of a rare metastatic location from HNSCC, thus expanding our knowledge of OPSCC, but also provides evidence for the local treatment of patients with metastatic HNSCC. The combination of immunotherapy with targeted therapy, chemotherapy, radiation therapy, and surgery may be the direction for future exploration (14).

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-1744/rc

Peer Review File: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-1744/prf

Funding: This work was supported by the Beijing Kangmeng Charity Foundation (No. KM222004).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-1744/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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(English Language Editor: L. Huleatt)