Management of Primary Mediastinal Yolk Sac Tumors: A Single Institution Experience with 10 Patients

Background: Primary mediastinal yolk sac tumors is a kind of primary mediastinal non-seminomatous germ cell tumor . The current treatment strategies in primary mediastinal non-seminomatous germ cell tumor is neoadjuvant chemotherapy followed by residual mass surgical resection . We reviewed our institutional 5 years' experience with Primary mediastinal yolk sac tumors who treated with platinum-based neoadjuvant chemotherapy and extended resection. Methods (cid:0) We experienced 10 cases of Primary mediastinal yolk sac tumors from October of 2014 to October of 2019. 7 patients received preoperative platinum-based chemotherapy followed by surgical resection of residual mediastinal mass. The other 3 patients were received initial surgical resection without preoperative chemotherapy. Results (cid:0) R0 resection was achieved in 8 patients (80%), and R2 resection was in the other 2 patients (20%). All the 7 patients with neoadjuvant chemotherapy were R0 resections, however all of them had viable tumor in their surgical specimen. Morbidities after surgery occurred in 2 patients, including 2 pneumonias ,1 type I respiratory failure and 1 acute left heart failure, and They were died within 2 months after surgery. At the time of writing ,3 patients are alive without evidence of disease,7 patients died , of which 5 patients have died of tumor-related causes and 2 died of postoperative complications. 8 patients were included in the follow-up. Among them 7patients experienced progressed within one year. 8 patients were included in the follow-up,mPFS and mOS in 8 patients were 3.7 months (2.6-41.3m) and 23.15 months (8.6-41.3m) , respectively. The 7 patients with neoadjuvant chemotherapy followed by surgical resection of residual diseases, 2-year survival rate was 57.1%,The 3-year survival rate was 28.6% Conclusion: An aggressive, multidisciplinary treatment including neoadjuvant chemotherapy followed by residual mass surgical resection is the optimal treatment and can be associated with prolonged survival.

Most patients are young men.(3)They often present with elevated alfa-fetoprotein AFP and/or beta-hCG(β-HCG at diagnosis, (4)and a computed tomographic scan of the chest aways revealed a giant mediastinal mass.
PMYST carries a very poor prognosis. The optimal treatment for PMNSGCT is chemotherapy followed by radical resection for residual mass. (5,6)At some centers, surgery is considered even in cases of the rst-line chemotherapy with non-responders, because of dismal results with second-line chemotherapy. (7,8)Despite aggressive treatment, the prognosis of these patients is still poor. (9) Literatures on PMYST are rare. Here is a review of our single-center experience.

Material And Methods
A retrospective study of 10 patients with PMYST who underwent extended resection referred to the West China hospital,Sichuan University , from October of 2014 to October of 2019, were performed. Tumor response was assessed with the use of RECIST, version 1.1. The pathological diagnosis in the surgical specimen were registered by pathologist ( Figure 1 and Figure 2 ) .

Statistics
Survival data was calculated from the date of diagnosis, until their last known follow-up day, or date of death. Actuarial survival curves were calculated according to the Kaplan-Meier method.

Result Patient and Tumor Characteristics
A retrospective study of 10 patients with PMYST who underwent extended resection referred to the West China hospital,Sichuan University , from October of 2014 to October of 2019, were performed.Patients' characteristics are summarized in Table 1.
Radiographic and Pathologic Response to Preoperative Chemotherapy 7 patients experienced some degree of radiographic tumor shrinkage from the preoperative chemotherapy. 6 patients met the criterion for PR( Figure 3)and 1 patients had SD. 8 of the 10 patients (80%) underwent an R0 resection and 2 (20%) an R2 resection. All the 7 patients with neoadjuvant chemotherapy were R0 resections, however All patients had viable tumor cells in their surgical specimen.

Operation and Surgical Complications
Details of surgery and complications are outlined in Table 2. Morbidities after surgery occurred in 2 patients, including a postoperative pneumonia and type I respiratory failure in 1 patient, and pneumonia,a persistent sinus tachycardia and acute left heart failure in the other one. They were died within 2 months after surgery.

Recurrence and Survival
At the time of writing, 3 patients are alive without evidence of disease,7 patients died, Of which 5 patients have died of tumor-related causes and 2 died of postoperative complications. 8 patients were included in the follow-up, among them 7patients experienced progressed. 6 patients progressed mainly in the form of metastasis, such as lung, brain, liver, bone, 1 had experienced anterior mediastinum recurrence which was due to R2 excision. mPFS and mOS in 8 patients were 3.7 months (2.6-8.6m) and 23.15 months (8.6-41.3m) , respectively . The 7 patients with neoadjuvant chemotherapy followed by surgical resection of residual diseases, 2-year survival rate was 57.1%,the 3-year survival rate was 28.6%.

Discussion
The majority of Germ cell tumors (GCT) originates from gonad, whereas only 1% to 5% of all GCT may occur in the extragonadal places. Elevated AFP and β-HCG at diagnosis is seen in 90% of nonseminomatous germ cell tumor patients. (11) Serum AFP levels are useful for the diagnosis and may guide treatment. In our report, AFP information was available for 6 patients receiving neoadjuvant chemotherapy, which decreased after chemotherapy and elevated when the tumor recurred, but no one was approaching normal levels . All the 7 patients receiving neoadjuvant chemotherapy were R0 resection, however, the surgical specimen of these patients exhibited viable tumors.
Due to the rarity of PMYST , oncologists recommend treating this disease like testes NSGCT. Multiple clinical studies have proved that cisplatin based chemotherapy combined with surgical resection of residual diseases is one of the most successful modes of multidisciplinary therapy (3,6,8). Firstly, PMNSGCT always located in the anterior mediastinum close to important mediastinal anatomical structures such as the great vessels ,the lung and the heart and so on . It is often impossible to achieve complete excision by initial surgery. Moreover, PMNSGCT are sensitive to rst-line chemotherapy, however, secondline salvage chemotherapy are ineffective, with only approximately 5%-10% of patients. (4,14). We recommend treat in a more aggressive way. Surgical resection was encouraged if resection was feasible after rst-line chemotherapy, even if Tumor regression did not achieve partial response. Finally, After cisplatin-based chemotherapy for PMNSGCT, viable tumor cells were still found in their surgical specimen (6). In our study, 7 patients underwent surgical resection after preoperative chemotherapy , of which 6 patients reached partial response and one with stable disease . However active tumor cells was still detected in all postoperative pathological specimens. Therefore, our data also support the view of surgical resection of residual tumor mass after chemotherapy.
In conclusion, PMYST is rare, and the prognosis is poor. A multidisciplinary aggressive approach including neo-adjuvant chemotherapy followed by surgical resection is the optimal treatment, but overall survival is still not satisfactory. We need to accumulate more experience and explore new treatments for this rare malignancy.

Declarations
Ethics approval and consent to participate the Biomedical Ethics Committee of West China Hospital of Sichuan University approved the study.

Consent for publication Not applicable.
Availability of data and materials All data generated or analysed during this study are included in this published article.