Patient B is a 76-year-old white male who presented with microscopic hematuria in 1986 on a routine urinalysis and a diagnosis of left RCC was made by imaging. He then underwent nephrectomy for a 7 × 6 × 5.5 cm tumor extending though the fascia into the perinephric fat. He did well until March of 2006 when he had a routine chest X-ray that showed new lung nodules and a CT scan was ordered. A large retroperitoneal mass posterior to the stomach measuring 10 × 9 × 8 cm was also found along with bilateral lung nodules, with the largest lung lesion measuring 2 cm. Biopsy of the retroperitoneal mass confirmed RCC. MRI of the brain and bone scan was negative. He was seen for the first time at our institution in April of 2006. He was determined to be a candidate for high-dose IL-2 (600,000 IU/kg). After 8 weeks, he did show some response, but was only able to tolerate half of cycle 2 and he declined further IL-2. He was then started on sorafenib and had a minor response at all disease sites until CT scan in January 2007 after 24 weeks showed progression. He was then switched to sunitinib 50 mg daily for 4 weeks of a 6 weeks cycles, and after 12 weeks on therapy had a significant response which he enjoyed until week 54 when CT scanning showed marked disease progression. Sunitinib was discontinued and in January of 2008 he was started on temsirolimus 25 mg IV weekly. He required a 20% dose reduction for thrombocytopenia and oral ulcers. He remained on temsirolimus until April of 2008 when he developed symptomatic mTOR interstitial pneumonitis, so temsirolimus was discontinued. His disease continued to progress off therapy and in October of 2008, bevacizumab 10 mg/m2 given every 2 weeks was started as fifth line therapy. After 24 weeks of treatment the patient was found to have a pulmonary embolus. Lovenox was started and bevacizumab was continued without incident. At the time of submission, the patient's disease has remained stable after 72 weeks of bevacizumab. He has continued to work full time as a maintenance man.
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.