Patient A was a 73-year-old white male who was diagnosed with RCC in 2000 and subsequently underwent a left radical nephrectomy. He went on to have multiple locoregional recurrences in the nephrectomy bed and in the lower pole of the right kidney. By January of 2007, he had involvement of the pancreatic tail and the left adrenal gland as well. He was evaluated at our medical center in March of 2007. He was restaged at that point and it was confirmed that he had no disease outside of the abdomen, so he was offered radical resection of his disease with curative intent by surgical oncology, but the patient declined. Therefore, he was started on sunitinib 50 mg daily for 4 weeks of a 6 week cycle, and an MRI in July 2007 showed decrease in the size of the tumor in the left renal bed and the pancreatic mass and right renal pole mass remained stable. Imaging after 24 weeks of sunitinib showed stable disease in known sites. His disease remained stable until imaging performed in April of 2008, after 36 weeks of treatment, showed clear enlargement of the renal fossa mass. The patient was then started on temsirolimus 25 mg IV weekly for second-line therapy. The patient had thrombocytopenia, worsening of lipid profile, and elevated blood glucose levels on temsirolimus that required a 20% dose reduction. After 12 weeks, CT scan showed pneumonitis consistent with mTOR inhibitor induced pneumonitis, a possible new lung metastasis, and progression of disease in the liver and renal fossa. Single agent bevacizumab 10 mg/m2 given every 2 weeks was started for third-line therapy and restaging every 3 months showed continued stable disease. The patient enjoyed 12 months of stable disease on single agent bevacizumab. It was stopped despite stable disease due to development of osteonecrosis of the jaw and patient request. The patient subsequently progressed rapidly and expired while off therapy.
A 60-year-old man was visited at the Alessandria Hospital Oncology Unit on August 2011 for a routine visit before a chemotherapy administration (FOLFOX scheme and bevacizumab), complaining of left mandible pain (VAS: visual analogue scale, score 6) and an oral mucosal break; the oral examination revealed a lingual-side bone exposure, 1 cm in diameter (no photo available). Four weeks before, he had started treatment with chemotherapy associated with bevacizumab for the second time.\nHis cancer history had begun on February 2010 with the diagnosis of rectal cancer and lung metastases. He underwent treatment with pelvic radiotherapy and simultaneous chemotherapy (oxaliplatin and fluorouracil in a continuous infusion) and then rectal surgery (on July 2010); additional chemotherapy (FOLFIRI) was administered in August 2010. Some pulmonary metastases were surgically removed on November 2010 but residual disease was still present in a chest postoperative CT scan.\nHe received chemotherapy (FOLFIRI scheme) and bevacizumab (5 mg/kg day 1 every 14 days) between December 2010 and March 2011 (eight cycles over four months). Due to pulmonary progression of the disease, he underwent a short treatment with an experimental agent in another cancer center, suspended on July 2011 due to the diagnosis of brain metastases, treated with radiotherapy. He then started new chemotherapy (FOLFOX scheme) with bevacizumab again.\nHis dental history revealed that he had been submitted for left mandible third molar (3.8) extraction at a private dental office on January 2011 (during the first bevacizumab treatment) without notifying the treating oncologist; the patient complained about incomplete and delayed socket closure after extraction.\nOn August 2011, at an oncology unit visit shortly after the start of the second course of bevacizumab therapy (two administrations), a painful mandible bone exposure was noted and the patient was referred to the Alessandria Hospital ONJ multidisciplinary team; antibiotics (amoxicilline plus clavulanic acid 1 g every 8–12 h and metronidazole 500 mg every 12 h) in combination with a chlorhexidine 0.12% oral rinse were prescribed, with immediate pain reduction. Rx ortopantomography showed no signs of osteolysis but just the profile of the residual socket at the extraction site (). A CT scan without contrast showed a mandible bone cortical lesion in the previous tooth extraction site, 7 mm × 4 mm in size (a–c). Spontaneous expulsion of a bone fragment was referred by the patient two weeks later. The patient was not further visited by the ONJ multidisciplinary team due to death shortly after an episode of pulmonary embolism on October 2011.